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Alzheimer's Disease - Science topic

Explore the latest questions and answers in Alzheimer's Disease, and find Alzheimer's Disease experts.
Questions related to Alzheimer's Disease
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Alzheimer's disease is a devasting neurogenerative disorder that continues to affect millions of people every year. But despite its prevalence, there is no medications on the market to prevent the disease or reverse the damage it causes. I wish to hear what may be the best treatment options for the Alzheimer's disease.
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The word cure implies complete reversal of the symptoms, which is currently not possible for AD.
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I'm evaluating a 57 year old male with complaints of memory loss, and family hx of Alzheimer's (father). He produced a rather unusual cognitive profile that has me scratching my head. Any feedback/thoughts that folks are able to provide would be very much appreciated. This is a basic battery, and additional testing is obviously necessary. I will provide testing data in the form of percentile rank:
***I am particularly baffled by the discrepancy between verbal IQ and verbal fluency tests
WAIS-IV
Full-scale IQ: 73 (premorbid IQ estimate- 34)
Verbal comp. index: 37 (similarities-25, vocab-50, info-37)
Perceptual reasoning index: 73 (block design-91, matrix reasoning-63, visual puzzles-50)
Working memory index: 98 (digits forward-91, digits backward-95, arithmetic-95)
Processing speed: 55 (Symbol search-63, coding-50)
WMS-IV
Visual Memory: 55 (visual reproduction I-95, visual reproduction II-9)
Visual Working Memory: 87
Auditory Memory: 10 (logical memory I-25, logical memory II-5, VPA I-16, VPA II-16)
Immediate Memory: 47
Delayed Memory: 5
*** VPA II recognition: 10-16%
D-KEFS
Visual scanning-63
Number sequencing-75
Letter sequencing-91
number-letter switching-84
Letter fluency-98
Category fluency-99
Category switching-95
Color Naming-91
Word Reading-84
Inhibition-63
*** Aphasia screening normal
fine motor assessment-bilateral impairment, but he has carpal tunnel
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Hi Natalie,
Interesting profile. I think Dr Joy's response is on point and, to follow on from that: The change from the learning trials to delayed memory performance could be captured well perhaps by a process-based measure like the recency ratio.
Also, extra information could be gleaned from the logical memory test
Another question would be whether they are correctly suffering from depressive moods, or whether they have a history of TBI, which I am sure you have already covered.
All best,
Davide
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Currently we are working on a review that surveys the cognitive/neural mechanisms of tactile working memory. We propose a sensory recruitment model, which suggests that prefrontal regions interact with somatosensory cortex to encode, maintain and retrieve tactile working memory. Please leave your email address if of interests.
Thanks,
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I am interested in neuro leadership studies
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I need a stack of black and white .jpeg/.tiff/.jpg/.png images across time of either action potentials, neurons firing, or brain scans (comparing disease and normal brain, disease progression, etc.) that I can colorize and overlay for a project in a data visualization course. It wouldn't be published and only for submission to the instructor.
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Something like this for action potentials ?
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Hi all
I'm starting to research rating scales to assess symptoms of agitation or anxiety in patients with dementia. If you know any papers or resources Id be very grateful for suggestions
Kind regards
P.J.
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Many thanks for this. This is really useful!
P.J.
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Substance-P is an example of peptide neurotransmitter present in hippocampus, neocortex region of brain which involved in perception of pain. I want to know is any link between this neurotransmitter to Alzheimer's or other type of dementia?
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There most likely are many causes of AD.
One prominent theory is loss of autophagy. This dysfunction
allows deposition of tau protein. Rapamycin inhibition of the
mTOR pathway allows improvement in autophagy and repair
of damaged proteins etc.and suggests therapeutic effects.
Mitochondrial dysfunction is also involved. The loss of normal
cell function due to severe mitochondrial damage from various insults
ie ischemia, toxins, hyperglycemia, direct physical damage etc.
Cells die at an advance rate via apoptosis.
I love this topic....so much to learn
Lester Mandelker DVM
Fellow AAVPT
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HI,
i am having difficulties with staining for Phospho TAU in KA-induced animal model.
I am using free floating immuno histochemistry method.
I am using AT-270, At-180, AT-100, AT-08 antibody (1:200, 1:500, 1:1000)
I have tried antigen retrival (sod citrate ph6)
i have tried 3%H2O2
I am trying blocking next lets see..
And Doing DAB staining.
Can any one help me ..or is there any specific technique????
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Update: With all the trails and fails: iam still having difficulties with the staining of Tau in my Rats.
May be the chemical iam trying is not inducing tau hyperphosphorylation.
I need to think of new ways until iam 100% sure of it.
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Dear experts,
Hello, this is Jean who is new to use ADNI data + DTI data.
I downloaded Axial DTI data of AD & CN, and I drop those data in dcm2niigui, but it does not work to covert to 4d nil image.
So I checked the data and it has 2,714 of dcm, which is different from what I got in PPMI DTI files.
Is it a matter of axial dti files? or is there any other issue regarding this??
Thank you!
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Hi. Are you using the Windows version of dcm2niigui? If yes, then this may be your issue.
I suggest you use the Linux (or Mac) version of dcm2nii, or even better is dcm2niix. If you still have problems, then I suggest you use MRtrix3 (specifically the command called mrconvert).
How many dicoms are in the PPMI DTI files? If you know how many volumes there are supposed to be (number of diffusion directions plus number of bzero volumes), and multiply that by the number of slices per volume, then that will equal the total number of slices (dicoms).
Jerome
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I need EEG data of normal patients as well as those suffering from Alzheimer's disease for my research. Can anyone suggest where can I find these?
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The link which you have provided is not working to get the data. Please guide me to get an EEG database of AlzAlzheimer's Disease and MCI. If it required some kind of contribution, I can. Please reply
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The association of free radicals in the pathophysiology of chronic diseases like degenerative brain disorders (AD, PD, HD, Stroke) has been evident by a substantial research.
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I am using a CNN for MRI image recognition. After running the model I stumbled upon some strange outcomes (at least, to me they seem strange).
1. The accuracy is very low. I have a binary classification task and the accuracy is below 50%. I'm using MRI's but haven't been able to apply skull stripping. Can the irrelevant information in the pictures be so distracting that the model actually learns nothing? Some additional info about my data:
2. The model is not showing a normal learning curve (see graphs). Instead of a slowly increasing accuracy and decreasing loss, these values seem quite random. Again, I have tried many different models, most of them were not learning at all (the accuracy remained the same in every epoch), this algorithm does learn but I don't understand these outcomes. Can someone help me understand what my models does?
If more information required, please ask.
P.s. I'm fairly new to programming and neural networks in particular, so any suggestions (also for pre-processing techniques) are more than welcome!
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I've been testing my A-beta 25-35 samples with ThT assay on a black 96-well plate to monitor its aggregation state, the fluorescence in 3 replicate wells differ dramatically unless I pipette the wells right before assay. 
I've read about shaking the plate before each ThT assay, but I'm not sure in what ways this method helps, and how can I shake a 96-well plate sufficiently without spilling the contents?
Thanks!
Lin
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Hello!
Shaking delivers extra energy to your system - it can shorten the lag time
Best
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I find very interesting the idea that intestinal microbiota might influence brain development and behaviour. There are research groups or studies that explore a link between the gut miocrobioma and dementia? 
Thanks
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For decades the AD theory of accumulation of A beta plaques and phosphorylated tau tangles has dominated the research on AD. Notwithstanding the tremendous amount of exciting studies in the field, the progress to understand the cellular and molecular mechanisms underlying AD has not still yielded desirable treatment. Some researchers started to suspect that maybe there are other different or parallel unknown mechanisms to focus on in order to pinpoint the etiology of AD.
In this regard, a recent study has shown that the isomerization and epimerization of long-lived proteins prevent lysosomal degradation which result in the accumulation of dysfunctional lysosomes in neurons and lead to AD symptoms.
The team stated in their paper that: "Lysosomal failure caused by the iso/epi modifications documented to exist in both Aβ and Tau offers a direct connection between these observations and a potential new pathway to explore for the underlying cause and treatment of AD."
Now, this discussion forum is open to opinions and arguments regarding this new hypothesis, and possibly a comparison of other rival hypotheses about mechanisms or etiology of AD.
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These hypotheses are not mutually exclusive. Already Alzheimer himself has speculated that not the plaques and tangles are the cause of AD, but soluble oligomers of the misfolded Aβ protein. The microscopically visible lesions would then be only correlates, but not cause, of the disease. Perhaps, they could be a waste dump, where afflicted cells put the misfolded proteins in a desperate attempt to reduce the damage done by them. The failure of plaque-reducing antibodies to prevent disease progression could certainly be interpreted that way.
The role of protein modification (spontaneous or enzymatic) in the misfolding and aggregation of proteins in amyloidoses is a very interesting issue, and addresses the pathomechanism one step earlier, but perhaps independently of the question of oligomer/aggregate.
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As a health researcher I have been long concerned at the lack of proper diagnosis of Alzheimer's Disease in older adults that pervades the mental health field. Up to 92% of those suffering from memory disorders have been found to also suffer from hearing impairment, almost all of them un-/under-corrected. This renders any diagnosis of AD in an older adult inconclusive or over-diagnosed. My symptomatic charts comparing the behaviors arising from late onset AD and moderate hearing impairment in older adults have been published by NIH entities, yet the practice of disregarding the auditory component persists throughout the mental health field. How may be best to remedy this pervasive oversight?
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My feeling is that genetic influence is not as strong as some tend to believe. For instance, in cases where we find "the deaf gene", we find almost no offspring that are deaf. In combining my clinical (empirical observations in a case history frame) and objective research experience I find genetics influence but do not determine outcome. Environment added to generic influence is a much stronger and more reliable predictor. In fact, as we begin understanding the plasticity of genes, even within individuals, we see a huge range of generic expression over time---from genetic repair to genetic breakdown. The Methuselah Mouse studies bear this out quite well.
But getting back to the core question of hearing loss---no matter what underlying genetic influence we can today conclude that uncorrected hearing does indeed influence both identifiable cognitive behaviors and the underlying physical cascade that brings it on. It is so pervasive that in one (University of Pittsburgh, 1999) meta-study of 32 studies on Alzheimer's and hearing loss, that older adults that were diagnosed with dementia (Alzheimer's), 92% were found to have uncorrected hearing loss.
The research trail before that (Chartrand, 1990; UT-Austin, 1992; University of South Florida, 1996) was better explained and framed in subsequent studies, such as Brandeis University (2006, 2008, 2012) and John Hopkins (2011, 2012, 2014, 2017)--to name but a smattering of the evidence that dementia and uncorrected hearing loss are, for sure, bosom buddies of the first order. But who's paying attention? The entire clinical community of mental health remains, in my opinion, in blissful denial.
For that reason, I started this project to try to 1) alert my colleagues of this massive and critical oversight, and 2) invite more evidence--pro or con--from anyone wishing to shed more light on the subject. To-date, no one has introduced hard data proving the central theme of this project is in error. I appreciate all of your comments--and hope we do the bold thing by getting the word out, thusly: No mental health assessment of an older adult is valid or conclusive until their hearing acuity has been evaluated and any hearing deficiency corrected. Once that has happened, one may have confidence that the diagnosis is reasonably valid, all other factors being equal. But to treat for dementia without first treating the hearing loss represents, at best, professional and clinical negligence.
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My dataset consists of EEG electrode power features in all power bands(alpha, beta, delta..both relative and absolute) and source power features (obtained after sLoreta analysis) in addition to connectivity strengths between the different sources (brain regions). There are as many as 20k features in all.
If i have to predict disease (dementia) based on all above features, what approach will yield best accuracy on test sets? I initially thought that maybe i must fit seperate classifiers for each type of feature set (after dimension reduction) and then use the output probabilities obtained to write a meta classifier on top to predict the final disease state.
However, i think that may perhaps not be so great as all features are correlated (as source estimates and connectivity measures are obtained from the electrodes themselves). Is this correct?
I used KernelPCA to select a few components from the entire dataset and then run a classifier on top of the transformed dataset with cross validation. I get an accuracy of around 75% only on test sets. I have to improve accuracy atleast by another 15%. I used extremely randomized trees but the accuracy was not that much.
What other approaches can i use?
I am looking for a good discussion on possible approaches and/or a sample solution. Thank you.
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Yes, try these two out. With keras you can build deep learning models very fast.
In addition you can try to find even better features.
A hyperparameter optimization could improve your classifier. However, I would try this last. First find good features and a suitable model.
All the best for you.
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Hi everyone,
I am trying to detect Amyloid oligomers in brain tissue extract of APP mice by ELISA kit but the outcome is mostly undetectable.
I am using IBL-Elisa kit: Amyloid Beta (82E1-specific) Aβ Oligomers (ref27725) and I have problems detecting it. I homogenize 5-10mg of tissue in Tris buffer pH7.4 (20mM Tris; 140mM NaCl) with a pestle (not sonication).
I have searched for publications about this form of samples processing but I don’t get any clear suggestion about it.
Anyone knows if it is necessary some other protocol or previous-step for low-weight samples?
Any advice are welcome.
Thanks in advance!
Ángel
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Hi Santosh Jadhav , I have checked the link that you pointed me out but I need to assess low-molecular weight oligomers that coexisted with Abeta plaques and soluble Abeta40 and 42.
Thanks!
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Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a quite hot topic these days among those who are concerned with dementia, memory deficits and neurodegenerative diseases.
It has been suggested that LATE is distinguished from frontotemporal lobar degeneration (FTLD) with TDP-43 pathology based on its epidemiology.
What do you think about this newly recognized disease?
Any idea about the potential or promising diagnostic approaches?
Possible future biomarkers and mechanisms...
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There is a nice article in Nature Neuroscience 2019;22:65-77.... "TDP-43 extracted from FTD brains displays distinct aggregate assemblies and neurotoxic effects."
They showed that FTD-TDP type A patients were more likely to manifest signs of behavioral variant FTD, and that FTD-TDP type B patients were more likely to manifest signs of the motor neuron variant of FTD, while the FTD-TDP type C patients showed signs of semantic dementia.
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We are trying to replicate the endogenous tau found in TgF344 AD rats (Cohen et al. J Neurosci. 2013 Apr 10;33(15):6245-56. doi: 10.1523/JNEUROSCI.3672-12.2013). We have used many antibodies - CP13, AT8, MC1, PHF1 - with DAB &/or tyramide booster, and haven't found anything. Please let me know if you have tried anything that works.
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Hi Claire,
According to my experience pTau in such models is often not as you would expect and comparable to a human AD brain. Typically you should also find hyperphosphorylation of some neurites within neuritic plaques. What could help you is using TrueBlack as a quencher for autofluorescence and then label with MOAB2 + pThr231 Tau [ EPR2488]. This one may be less prone to conformational differences from fixation procedures, and if you are using citrate buffer steaming (if FFPE) you might be able to increase labeling results. pThr231 is typically also found naturally to some extent, so you should also know from WT that the labeling works. Beside that this p Site is early hyperphosphorylated in AD and is typically also one of the first to become positive in amyloid/PS models.
Just as idea,
Good luck,
Daniel
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I am working on immune reaction in Alzheimer's disease in mouse models at UCL. Currently I am doing co-immunostaining with antibodies against Iba1 (green) and CD68 (red).
My question is:
How to evaluate whether the microglia cell is activated or not? The signal varies quite highly, and can be either punctuate or globular, either in the cell body or in the processes or both.
As it is a phagocytocic marker I am aware that there is variation. However I am unsure of where to draw a line between unactivated to activated.
Thank you for advice!
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Thank you Priya Prakash, what is the thickness of the mice brain tissue you suggest for CD68 staining? And if they need to be cryostat, microtome or vibratome sections?
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Please tell me where can I get EEG data for Alzheimer's disease , because I am working on designing an automatic diagnosis system for detecting diseases.
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As part of our research work in developing machine learning framework for dementia analysis using EEG data, we have made the source code and data (both AD and Controls) publicly accessible. The links are in the acknowledgement section. I hope this will be useful to you.
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Should i exclude them from analysis? does LPS iP injection increases Thigmotaxis behavior?
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I would agree with the previously provided answers, however I would inquire about the following: 1st what is the interval between injection of LPS/Control and water maze? 2nd you stated that you have controls, did their injections schedule match? If both Controls and LPS injected mice both display equal amounts of thigmotaxis, it is possible that the injection itself could be the issue not so much the LPS. Mice inherently more stressed and water maze results vary greatly between laboratories. The injections may be the cause of stress can you do the following to reduce the stress of injections: 1) give LPS or Control injections after maze, if it is daily injections or 2) if you could give injections well before testing e.g. 24/48hrs before start of maze. As for exclusion, did you have an a piori parameter for exclusion? If not than no they should not be excluded. A easy test would be to have a single day of visible platform performance after hidden platform and probe testing. Once an a prior exclusion factor is established, such as failing the visible platform test, only those animals can be excluded. As in all animal behavioral testing, consistency is paramount to good data.
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Hi,
I'm looking papers about diet intervention in patients suffering from Alzheimer disease. Have you seen any?
Thanks,
Mikołaj
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There is much less on diet and progression of AD than on diet and the onset of AD. However, here are a couple of recent articles that you may find interesting and
Regards,
Simon Young
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Dear All,
I am interested in using machine learning to analyze MRI data in order
to extract pathological changes for neurodegenerative diseases (i.e Alzheimer's, Huntington's )
Can someone please give some advice on what (bioinformatic,statistical) methods from your experience would be best for an initial analysis and to extract disease specific features ?
Also what would be the most useful platform and what visualization tools or popular packages are best for data extraction and presentation in this case ?
I have about 500 samples from Philips and Siemens scanners ... Could you also suggest the processing power that I would typically require ... for example If I want to train my data and create module or signature prediction algorithms and what MRI parameters would be most informative in each case ( i.e FLAIR, DTI ?)
Any help would be greatly appreciated
Regards
Anastasios
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I am currently collecting brain tissue from HFD/STZ induced T2D mice. I am noticing a trend for lower brain weight in the more severely diabetic mice. I am aware of the impact T2D can have on cognitive function and may be a contributing factor in Alzheimer's development. I am also aware that late stage Alzheimer's patients have significantly less brain mass.
Can anyone provide some insight or link to some papers that address this?
Thank you
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Please check
Susan J. Burke, Heidi M. Batdorf, David H. Burk, Robert C. Noland, Adrianna E. Eder, Matthew S. Boulos, Michael D. Karlstad, J. Jason Collier
J Diabetes Res. 2017; 2017: 8503754. Published online 2017 Sep 6. doi: 10.1155/2017/8503754
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As previous research indicates that the bilingual people are more resilient to dementia, developing several years after the monolingual, so is it a proportional correlation?
Is more languages practice associated with further reduction in dementia future risk?
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Dear Anton
Exclude other metabolic issues like hypothyroidism or encephalopathy due to metabolic errors also mild concussion may cause some psychiatric manifestations including depression which may then mask her cognitive abilities and reserve and appear as if declining cognitively while the fact that she is depressed so is not communicating or refusing to.
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The age of onset of HSP varies tremendously, ranging from very early in life up to old age.
There are various mechanisms causing HSP, summarized
e.g. in Fig. 2 of S.Klebe, G.Stevanin and C.Depienne, Revue neurologique 171 (2015) 505.
There should probably be different reasons for different cases.
If some gene (protein) is wrong, one can imagine that trouble starts right at the beginning.
In a late onset case one could imagine that some kind of toxic substance ('Placques' in Alzheimer disease e.g.) accumulate over time and cannot be removed fast enough.
 
Does anyone have more concrete ideas about what is going on?
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Hereditary spastic paraplegia is a heterogeneous group of disorders, the predominant signs and symptoms of which are lower extremity weakness and spasticity. Defects in various pathways (e.g. axon transport, mitochondrial function, myelin formation, ER-stress response, endosomal trafficking, Ubiquitination, etc) have been shown to cause this disorder. However, all HSP subtypes are characterized by corticospinal tract axonal degeneration.
Regarding the age of onset, there is indeed a wide variability between different subtypes and even in one subtype within a family. For instance, a huge variation in the age of onset (6–60 years) has been reported in an Italian family with a mutation in Atlastin (S259F) [Smith, Bradley N., et al. "Four novel SPG3A/atlastin mutations identified in autosomal dominant hereditary spastic paraplegia kindreds with intra‐familial variability in age of onset and complex phenotype." Clinical genetics 75.5 (2009): 485-489].
We certainly need large scale genomic studies in order to make some progress in understanding the underlying pathological mechanisms involved.
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When plotting a bifurcation diagram in nonlinear dynamics, the axis x displays a given phase parameter. Are there examples in which the phase parameter stands for time passing (for example, from the value T0 to the value T200 seconds, or months, or years)?
Thanks!
To make an example, I was thinking to something like the one in the Figure below, concerning the phase transitions among liquids, solids and gases: if you leave, e.g,., that the temperature raises of one degree every second, can we say that the axis x displays time (apart temperature values)?
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see my theory
In which I discuss the possibility of rapid movement given specific situations arise in my theory... You speak of some in your question...
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I am trying to use IL-6 and CD163 as a microglia marker in Alzheimer's Disease mice model, but it seems not to be working. If anyone has succeeded before, please give me some suggestion about the detailed protocol? Thanks a lot!
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You could try to use P2YR12, it is microglia- specific in brain (resting microglia) and the expression in activated microglia is dramatically decreased.
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I am not sure if we are supposed to change staining protocol for different mouse strains, but I am having difficulty staining (free floating immunofluorescent staining) on my 5XFAD mouse brain sample.
Basically, I see high background staining (auto-fluorescence) when I use confocal.
My samples were previously exposed to 4% PFA (perfusion + overnight post fixation) then washed and stored in 1XPBS with 1% sodium azide.Tissues were embedded into LMP 3% agar and sliced (50 um), using vibrating microtome.
So far I've tried...(***blocking solution contains 0.1% tritonX-PBS)
  • 10% FBS blocking with donkey anti-mouse secondary
  • 4% BSA blocking with donkey anti-mouse secondary
  • 5% horse serum blocking with donkey anti-mouse secondary
To make it clear, there is no confocal issue. So far I've never encountered this problem when I stained on other mice.
Any suggestions (protocol/reference) would be much appreciated!
Thanks,
Yuka
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Hello Yuka, I think you had quite some input from Aparajita. I'll just try to give you some theoretical background...
As far as I can see you are using a primary Ab raised in mouse on mouse brain. A good perfusion will of course remove most of the blood from the vessels in the brain, still when using mouse primaries you will often have to deal with the natural reactivity of the secondary Abs with the residual mouse Abs in the brain, so unless your primary is very strongly binding to its epitope you'll have to cope with many stripes that light up all over your section.
Second issue is autofluorescence. As already mentioned it is highest in the green and often found also in the red. Still if you have a weak Ab it might not be wise to use a red or far red conjugation, since the photosensors arrays on the modern digital cameras are built dedicating two photodiodes to the green and only one to red and blue, so any emission richer in the green spectrum will result double the intensity than an equal emission in the red or the blue. And confocal microscopy loses so much signal in favor of image clarity and resolution, probably more than 80%, so you need good signal and good detection, as Aparajita already pointed out.
Autofluorescence is given by blood and many other unsaturated or aromatic substances found in the cells, as well as from free(unreacted) aldehydic groups from the fixation, so you do have some chemical treatments, typically via red-ox, to quench them before you start blocking. One possibility is, as described, H2O2. This should reduce at least blood fluorescence. Other possibilities, more specific for reducing aldehydic groups from formaldehyde (bur also sugars and other substances) are 100 mM NH4Cl or 100 mM glycine, 30 min to 1 hr at room temperature. Finally if you need to be really harsh you can use NaBH4, a strong reducing agent for aldehydic, chetonic, carboxylic, and ester groups, that you have to prepare fresh at 1 mg/ml and apply immediately to your sections, 3x20 min (it will fizz evidently, producing gas).
Other issue might be the penetration of your antibody in the thick tissue. For this we use to complement the blocking and the antibody dilution solutions with 1-4% DMSO (depending on the thickness and coarseness of the tissue, in your case 1-2% should be enough). DMSO is technically non-denaturing for proteins, but in substituting water molecules alters slightly their structures due to its greater steric hindrance, producing holes in the thick extracellular matrix and fixed cytoplasm, allowing your Abs to penetrate up to 2-3 layers of cells into the slice. Just a note on the use of 20% DMSO mentioned by Aparajita, seems high, we tried it without particular success on entire embryonic diaphragms and we went back to our standard 2% provided also with the Abs, but I suppose the idea is the same.
Concerning the blocking, you tried already a few things, from very stringent (10% serum) to mild (4% BSA)... if you didn't observe any change, it means that's not your issue: if you lose signal with stringent blocking it means your Ab needs less blocking, if you have too much background with low blocking it's the opposite... sometimes you'll need to look for the compromise. But if you didn't observe differences, then blocking is not an issue for your specific Ab, and you can stay low, or have no blocking.
Last issue are the conditions at which you incubate your Ab. The kinetics and thermodynamics of Abs binding are pretty complex and unpredictable. Three factors can play an important role: pH, temperature and time. Most Abs will work optimally at any pH, but some will prefer pH 8, while others will prefer pH 7.4... if you have problems with a staining, you should try if pH makes a difference. Secondly temperature: typically one incubates Abs O/N at 4 °C. If all works well, fine, if not, try O/N at room temperature instead. Sometimes it also helps 1 hr at 37 °C. And time... although O/N is working most of the times, we have Abs that need 2-5 days, either at 4 °C or at RT to give enough signal for confocal or super-resolution microscopy.
Final point, it sounds a bit odd that a specific mouse line should behave differently form others. I would look more into your procedures. If you only tried on one 5xFAD mouse, it is possible that for example the perfusion was not very successful and you have more blood left in the vessels... Also the plaques, although insoluble aggregates, should not particularly affect a staining (although you didn't tell us what you are staining, if it is in the plaques themselves, in the matrix or in the cells!).
Good luck!
Pietro
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While breeding 5xFAD, there is Pde6brd1 mutant homozyous which cause retinal degeneration .
That mutation degenerates eye rod cells which detect bright and dark.
Can I use that mouse in morris water maze?
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Hi Sooyong, excellent question. The work of criscuolo et al 2018 ( PMID: 29735432) suggest that these mice perform poorer on the water maze test as early as 1.5 months. If you would like to study the behaviour of these mice without the confound of poor vision, you can try using this strain of 5xFAD https://www.mmrrc.org/catalog/sds.php?mmrrc_id=34848 where the Pde6brd1 mutation has been bred out. This strain maintains fairly good vision but they also tend to develop brain plaques later in life ~6 months as opposed to 1.5 months.
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I want to check cell internalization of Abeta (1-42) peptide w.r.t. However, I do not have fluorescent labeled Abeta peptide to perform this experiment. Is there any other ways by which I can monitor the same.
Or is there any protocol to tag fluorescent dye to a peptide after cleaving it from the resin???
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Hi Jahnu, you could always do the classical internalization assay using radiolabeled I125, C14 or H3 ligand.
FlowCy and confocal are subjective for quantitatively determining internalization. Using radiolabeled ligands gives you an absolute quantitative value.
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Apart from the trails test can anyone suggest tests that are done to check someone’s processing speed in dementia patients please.
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I hope you find it useful
Digit Cancellation Test:
Zazzo R. Test des deux barrages. Actualités pédagogiques et psychologiques . Neuchâtel, Switzerland: Delachaux et Nestlé; 1974.
Pattern Comparison Test:
Salthouse TA Babcock RL. Decomposing adult age differences in working memory. Development Psychol . 1991;27:763–776.
Regards
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I am interested in doing an ROI-based analysis of ADNI FDG-PET data to examine regional metabolism in their control group. I am using a coregistered volumetric MRI to create anatomic ROIS and exporting these as masks to use on the PET data. Since I'm using ROIs created from each subject’s own MRI scan, is it still necessary to do a partial volume correction, or is that something you do only if you’re warping everyone’s images into a common space (e.g. MNI)? And, if I need to do partial volume correction anyway, is it a reasonable alternative to simply erode each MRI-based ROI mask by 1 voxel all around to avoid the issue, instead of doing a more complicated partial volume correction method (e.g. segmenting a coregistered MRI image, calculating a CSF dilution factor and then correcting the raw time-activity curve of the PET in each region)?
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My mistake on my previous answer I wanted to say that this method estimates an average radioactivity and not a homogeneous for the two background regions.
Sorry for my mistake and any misunderstanding caused.
In addition to my previous answer, the Müller-Gartner method will only correct for one region (most of the cases the GM) and will not treat the other regions of the brain.
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Can neurofibrillary tangles (NFTs) be visualized with Congo Red? What would be the difference between various staining methods used for this (ie. HE, silver stainings,...)? What's the best one?
Best,
Jan
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Gongo red is specific for amyloid and easier to do than a silver technique. H&E is all general "stain all(most)" tissue types of technique to give an overview of what is happening. An LFB/CV luxol fast blue counteren with C violet is another good easy CNS stain.
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I can't find any interesting study showing such dependence reliably. Maybe someone know a interesting paper?
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Several studies have identified metals such Pb, Fe, Al, Cu and Zn in AD pathogen sis. Metal ions are known to catalyze the production of free radicals and induce mental retardation or dementia, Since several dietary polyphenols are known to chelate metals, their routine use may also be protective against the onset of AD. For details consult J Alzheimers Dis. 2010 Jan: 19 ( 4 ) : 1123 - 1139
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Dear all,
Currently I am working on Alzheimer's disease. In the literature i had noticed the staining of both Cresyl violet and H&E for histopathology studies. what are the things we can differentiate through different types mentioned stains.
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To see neuron/glia in hippocampus, Niissl stain (Cresyl voilet) is the conventional one.
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Which suitable cell lines for studying Alzheimer's disease ? Thanks for answers in advance.
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I not am sure I quite understand what you mean by "Alzheimer-formed cell line".
Anyway, APPswe-N2a is neuro-2a cell line stably expressing the human APP Swedish double mutations at codons 670 and 671 of APP-770 in N2a cells. The Swedish mutation is a well-researched, if not the most-researched, Alzheimer's disease mutation. These cell lines are quite popular in the A.D research community and can easily be obtained from numerous scientists all over the world. So, I suggest you look for scientists working with these cell lines in countries around you and make a request from them, I am sure they will be glad to send you some vials because I don't know if these cell lines are commercially available. Good luck!
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Neuro fibrillary tangles are formed by the aggregation of tau protein which ultimately results in the death of neuron, and beta amyloid is formed by the cleavage of beta secretase.
Here what happened to the synthesis of alpha secretase, in Alzheimer's patient is there any competition between alpha secretase and beta secretase or alpha secretase is completely absent ?
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Finally, a Winner for Alzheimer's? Anti-amyloid Agent Shows Promise
Pauline Anderson
July 26, 2018
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CHICAGO — Positive results for an anti-amyloid agent in patients with early-stage Alzheimer's disease (AD) is drawing praise, but experts are calling for caution.
Results from the new phase 2 study showed a statistically significant reduction in brain amyloid with a high dose of BAN2401 (Eisai Co. Ltd/Biogen Inc) at 18 months.
In addition, the study showed a dose-dependent, statistically significant, and clinically meaningful slower decline in cognition and function with the highest dose compared to placebo.
"This is the first large clinical trial to support the amyloid hypothesis," Lynn D. Kramer, MD, chief clinical officer and chief medical officer, Neurology Business Group, Eisai Co, Inc, told a press briefing.
The study was released here at the Alzheimer's Association International Conference (AAIC) 2018.
Unique Trial Design
The multicenter study included 856 patients with early AD (mild cognitive impairment due to AD or mild AD dementia) and amyloid pathology confirmed by positron-emission tomography (PET) or cerebral spinal fluid (CSF) tracer.
At baseline, the mean Mini‒Mental State Examination score was 25.6; the mean Clinical Dementia Rating Scale‒Sum of Boxes (CDR-SB) score was 2.9, and the mean Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) score was 22.2.
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I am performing western blot analysis to detect the protein expression changes in the brain tissues from several neurodegenerative diseases (e.g Alzheimer's, Parkinson's) as compared to normal control (age-matched). In your experience, which is a better loading control - GAPDH, ßActin or α/ßTubulin?
If you are aware of any articles that addresses above question, please do share.
Thank you for your feedback!!
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Hi,
The journal of biological chemistry (JBC) declares in the editorial recommendations that "Normalize signal intensity to total protein loading (assessed by staining membranes for total protein) whenever possible. “House-keeping” proteins should not be used for normalization without evidence that manipulations do not affect expression.".
For more information the JBC indicates:
Interestingly, Dr Oh informs that journals often openly state that of the western blotting normalization methods they prefer, total protein techniques are at the top of the list. In fact, since 2012 when it was first introduced, stain-free total normalization has appeared in over 800 publications (almost 500 of those appearing in 2017).
For more information
I suggest as total protein quantification method the membrane staining with Ponceau S., Coomassie Blue or Amido black.
Best regards.
Mauricio
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Currently we are working on Alzheimer's disease. From literature we unable to get conclusion regarding the usage of coordinates, as i have find out lot of difference in the coordinates from article to article.
Ex 1: 4.8 mm anterior to posterior (AP) Bregma, 2.2 mm mid to lateral (ML), and 3.0 mm dorsal to ventral (DV).
Ex 2: −3.6 mm anterior‑posterior to the bregma, 2.4 mm lateral to the sagittal suture, 2.8 mm dorsoventral.
Ex 3: −0.8 mm antero-posterior from bregma and ±1.5 mm medio-lateral from the midline.
etc.,.
I will be using Amyloid beta and Streptozotocin as an inducing agent.
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Most individuals have targeted the rodent dorsal hippocampus for learning and memory work, since of course the case of H.M., disregarding the sloppy monkey work that quickly followed trying to replicate H.M.'s amnesia. The work picked up again with David Olton's hippocampal disconnection lesion work in the mid-seventies, using the radial-arm maze, fining that the dorsal hippocampal lesion was just as effective as entorhinal and dorsal hippocampal lesions or entire hippocampal lesions. LTP also had its heyday in the dorsal hippocampus,regardless of whether the perforant-path Dentate or CA3 to CA1 pathways were examined. Possibly most relevant is Richard Morris' work of the 80s onward, shifting from hippocampal lesions to intrahippocampal infusion of N-Methyl-D-aspartate (NMDA) receptor antagonists, A-Phosphono-valeric Acid (APV), used to block both LTP and learning. Coordinates from this work in the Wmaze may be the most relevant. Encompasing his J.Neurosci. publications and his slew of Nature papers.
Matching strain and size is important, and Morris' has a J. Neurosci. paper where India Ink was also infused intrahippocampally to catch the spread of the infusion and document it in Histology to show restriction to Hippocampus, as well sufficient spread within the dorsal hippocampus. Others, have used Prussian Blue reactions during histology to passing current through insulated injection cannulae to again mark the infusion sites.The intracerebral infusion work was important with the staining, beaus it permitted separation of mechanical damage from cannulae implantations from that of the infusate.
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Hi:
Does anyone know if it is possible to detect mRNA expression levels of Tau variants (e.g. Tau40, Tau42) in non-cerebral cell lines such as HUVEC and THP-1? mRNA expression levels can be detected in transgenic mice expressing such human variants, but I am not sure if it possible in cell lines. Given that Tau is a microtubule‐associated protein found in epithelial cells (an other types), it is possible that Tau expression may be up/down regulated depending on the cellular circumstances, but I am not sure if the splicing events related with Alzheimer has been observed in cell lines and detected by qPCR.
Thank you in advance,
Rafael.
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Thank you Muneeb and Santosh for your suggestions.
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Hello,
I am Henrique. My current project is Animal-Assisted Therapy for Alzheimer's Disease patients using Virtual Reality.
I am currently validating the effects of a designed tool. I am trying to find any tool or questionnaire that could address the pre and post intervention stress level or agitation level. If you know any other tool for any other interesting aspect other than stress or agitation that could be related in some way please also mention.
The intervention consists in having the subject try out an application during 10-15 minutes and then evaluate if there was any change in mood, stress or agitation, etc.
I am new to research so I have not much experience in searching or using these evaluation tools/questionnaires.
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Hi Henrique,
We have used the Depression Anxiety Stress Scales (DASS) in quite a few studies and it shows good psychometric properties. Furthermore, it's free and you'll get additional readings (depression and anxiety) in addition to stress. Here is the website from where you can download the scale and obtain additional information. Regards. Rodrigo.
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I want to test the GSK3 activity in neuronal cells. Since the isotope is not authorized in our lab, I wonder whether there is an isotope-free  method for detecting GSK3 activity.
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Thanks for the alternative methods and sugestions from James and Taussif. They were very kind and I will try to choose the best that I can do. I will tell you the results. Thanks a lot.
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Hi, I want to quantify total tau, phospho tau and tubulin in the axon and dendrite of hippocampal and cortical neurons by Confocal microscopy analysis. I'll appreciate if you could suggest me the method to distinguish axon from dendrites, and the method to quantify them using imageJ software.
I have attached the image file/picture I scanned using microscope (red channel: total tau, green channel: tubulin, yellow channel: phospho tau). The image is focused on neurites.
Thank you.
Sincerely,
Saroj
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Hi Mona and Muneeb. Thank you so much for your suggestion.
I was wondering if the filaments with microfluids chambers are axon, I could differentiates axon. I took the thick filaments which are at proximity of soma (cell body) as dendrites. So I am confused in the selection appropriate axons. In the image I have attached, soma in not under focus as I scanned the image with prim focus on neurites (axon and dendrites). I have already taken and scanned images for only cell body(soma). That's why I need to distinguish axon in the image I have attached. Your suggestion would be highly appreciable. Thank you once again.
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I have done Radial arm test for rats of 5 groups, with 10 animals in each group. I am trying to analyse the results through graph pad prism. On what basis we have to go for selection of either Bonferroni or Turkey test?
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First of all, what is your measurement? Time taken to complete the maze? It is helpful to first get a feel of what your data looks like. Most researchers ignore the most important first step in statistical analysis, descriptive statistics, and instead opt for going straight into inference on assumptions which may not hold i.e that your data is normal. I highly recommend that you learn to use R. You should plot out your data and see what it looks like: is it skewed, are there outliers, what is the mean and standard deviation? I presume you wish to conduct ANOVA? Remember that the tests rely on an important set of assumptions which you should test (easily in R), otherwise your results will be invalid. I recommed that you find a good textbook or document that will guide you through the process. Don't rush in a bid to get "good" results. Statistical analysis takes time and thought, and you will be better off as a researcher for knowing how to do it properly.
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I have to use an animal model of Alzheimer's disease that shows beta amyloid plaques and also Tau hyperphosphorylation but the only model that I found has a 129 background and I need a model with c57bl6 background. Tks
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If you indeed backcross, consider using Speed Congenic approac. Will save you time. To read about it:
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Is there any process by which we can detect early stages of Alzheimer?
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Back home, they say if someone can't find his car key (forgot where he put it) this will be the first sign.
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I am going to work on geriatric sporadic Alzheimer's disease. Tripple transgenic mice model is good for famillial alzheimer's disease but it is not a good model for sporadic alzheimer's.
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Hi Nageeb, unfortunately animal models of diseases dictate that they show the full blown pathology within a year if you are looking to get funded.
An animal model of sporadic AZ might be out there, but it will probably not get funded since they are sporadic and non-reproducible unless you have a large cohort of animals.
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I need a non-transgenic model for Alzheimer's disease in order to use it to test the efficiency of stem cell therapy on neuro-degenerative diseases.
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It has been suggested that AD is more common in human female population and disease progression is more aggressive in female 3xTg mouse model. However 3xTg males seem to be used quite often in studies as well.
I'm planning to do some behavioral tests on 3xTg mice, there are reports on hyperactivity in aged females, and that estrus cycling may confound assessment of disease-related behavioral dysfunction. I'm not sure if there are any other special concerns with this model regarding the choice of gender.
Also Jax warned that male 3xTg transgenic mice may not exhibit the phenotypic traits originally described, thus I might have to use females since I’m going to purchase from Jax.
Does anyone have experience with this model? How are the females doing in behavioral tests and what are the concerns?
Thanks.
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ovariectomized females to eliminate the cycle effect?
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Alzheimer's disease
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Please allow me to respond succinctly, since there are still no effective ways of treating Alzheimer's disease. The reason for this situation lies in the lack of specific knowledge about the key mechanisms for the development of this neurodegenerative process. Beta-amyloid and tau-protein disrupt the functioning of neural networks in the brain. Inactive nerve cells begin to die. And most often only at this late stage clinicians diagnose Alzheimer's disease. In recent years, scientific articles have appeared, the authors of which are trying to use stem cells to fill the number of dead neurons. In fact, this is a situation where in this way clinical specialists try to increase the number and potential of "normal" neurons in the brain. But this is basically a palliative approach. It is necessary to find the mechanism of the disease development.
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Is there only one pathway of cholinergic available for Alzheimer disease ? there may be a possibility of any other pathway for drug dilevery ?
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Hi. The glutamate receptors mediate excitatory neurotransmission in the brain and are important in memory acquisition, learning, and some neurodegenerative disorders. This receptor family is classified in three groups: the N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-kainate, and metabotropic receptors.
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I know magnetoencephalography (MEG) records magnetic fields-which are very small- produced by electrical currents in brain to map brain activities. how effective the external magnetic fields can be on the response? can we also use them (external magnetic fields) to change brains activity on a good way-such as improving memory?
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You answered your question. Yes, external magnetic fields affect MEG recordings and quite easily can make them useless. What MEG measures is extremely weak magnetic field induced from neuronal currents. Background (external) magnetic field is much stronger and it would be probably impossible to measure brain magnetic field if the MEG recording rooms were not magnetically shielded.
Regarding the second question, check out TMS (Transcranial magnetic stimulation).
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I am working with PPI network of Alzheimer's disease (AD) and type II Diabetes Mellitus (DM) . But I am facing difficulties to retrieve all risk genes predisposing to AD and DM. Some literature have focused on GWAS database, some have focused on candidate genes. Which method should I need to follow?
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I am working with risk genes for the obesity, as risk factor of cardiovascular diseases. I used GWAS by traits associated with the obesity, both anthropometric and biochemical. I generated the table with all related studies. Then I was filtering the data. For me it was important to obtain results obtained or validated on Caucasians. After this I understood that an ontology of traits would be necessary to exclude overlappings, e.g. results for 'lipid' trait and 'HDL cholesterol', excluding the one referred to more general trait in the ontology. This gives you one more outcome - you will know which pathways to analyze, so have hints on involved proteins! Then you may turn your attention to the candidate genes, associated genes etc, in order to check what might be missing. And complement ( but dont forget to to mention the source of each gene in your list, might be helpful in some cases). If you have your experimental data, you may try to "validate" them. Or you can check for microarray or RNAseq data, in order to check your gene list there and identify if reliable data are included regarding gene co-expression.
So, it may make your analysis heavier, but still you need a step to prove what you've obtained.
Good luck
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There are different types of diagnostic tests for Alzheimer's disease. as far as I know, one of them is positron emission tomography (PET) scanning. what exactly does cause the sign of the disease on a PET image? what percentage of Alzheimer's disease can be diagnosed by this procedure? do prescription drugs affect these signs after we take the test again?
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Hi,
Currently, International Working Group (IWG) and National Institute on Aging Alzheimer's Association (NIA-AA) has proposed several biomarkers as diagnostic criteria which includes cerebro spinal fluid (CSF) amyloid beta (Aβ) and tau, atrophy on MRI, glucose metabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and fibrillar Aβ burden on amyloid PET.
There are few regions, which acts as definite Hallmark regions for AD. You could refer to below attached papers.
(11)C-PIB-PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI)
Structural MRI and Amyloid PET Imaging for Prediction of Conversion to Alzheimer's Disease in Patients with Mild Cognitive Impairment: A Meta-Analysis
18F-FDG PET for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI)
FDG-PET for Prediction of AD Dementia in Mild Cognitive Impairment. A Review of the State of the Art with Particular Emphasis on the Comparison with Other Neuroimaging Modalities (MRI and Perfusion SPECT)
Biomarker-based prediction of progression in MCI: Comparison of AD signature and hippocampal volume with spinal fluid amyloid-β and tau
Biomarker-based prediction of progression in MCI: Comparison of AD signature and hippocampal volume with spinal fluid amyloid-β and tau
I hope these article will help you.
Further, regarding the medication you could look into these articles
Drugs for Alzheimer’s Disease: Are They Effective?
Pharmacogenomics and therapeutic prospects in Alzheimer's disease
Cholinesterase inhibitors for Alzheimer's disease
Gud Luck !!!!
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Manually annotating the datapoint of interest using simple edge detection or segmentation techniques for labeling won't be an ideal procedure?
So what's the suitable cost effective step that can be achieved here ?
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Dear Das,
There is no such recommended algorithm best designed for feature selection task. Rather you will have to test with several of them on your application and check for the best one. However, you may find some real applications of algorithms used recently in feature selection task in the following papers:
1. Suk, H. I., & Shen, D. (2013, September). Deep learning-based feature representation for AD/MCI classification. In International Conference on Medical Image Computing and Computer-Assisted Intervention (pp. 583-590). Springer, Berlin, Heidelberg.
2. Segovia, F., Górriz, J. M., Ramírez, J., Salas-Gonzalez, D., Álvarez, I., López, M., ... & Alzheimer's Disease Neuroimaging Initiative. (2012). A comparative study of feature extraction methods for the diagnosis of Alzheimer's disease using the ADNI database. Neurocomputing, 75(1), 64-71.
3. Liu, M., Zhang, D., Shen, D., & Alzheimer's Disease Neuroimaging Initiative. (2012). Ensemble sparse classification of Alzheimer's disease. NeuroImage, 60(2), 1106-1116.
4. Shi, J., Zheng, X., Li, Y., Zhang, Q., & Ying, S. (2018). Multimodal neuroimaging feature learning with multimodal stacked deep polynomial networks for diagnosis of Alzheimer's disease. IEEE journal of biomedical and health informatics, 22(1), 173-183.
5. Liu, X., Chen, K., Wu, T., Weidman, D., Lure, F., & Li, J. (2018). Use of multi-modality imaging and artificial intelligence for diagnosis and prognosis of early stages of alzheimer's disease. Translational Research.
6. Zhang, D., Huang, J., Jie, B., Du, J., Tu, L., & Liu, M. (2018). Ordinal Pattern: A New Descriptor for Brain Connectivity Networks. IEEE Transactions on Medical Imaging.
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Hello.
I am working on a project that may be of great benefit to people with Parkinson's or Alzheimer's Disease but I need some NMR work done on the product(s) to confirm that I have the correct molecule and to determine the amount of it.
I can provide the test material and both standards (a pair of diastereomers) as dried precipitates or in ethanol. A publication (20 years old) gives a complete assignment of the 1H and 13C NMR spectra of both molecules dissolved in chloroform. I'm pretty sure I can produce milligram amounts of the target molecule(s) but do not know how pure it is.
I've out-sourced a “feasibility study” for this NMR work but to continue with this (or any) CRO is too expensive. I cannot offer any contributions to your costs or university overheads. It is impossible to patent this.
I'm looking for someone with an NMR machine who is willing to help in return for being the second author on a paper (to be submitted to a suitable peer-reviewed journal) with the potential to be highly cited in the area of neurology and that might help millions of people burdened with neurodegenerative diseases.
If you are interested and have the machine and skills to create and interpret NMRs, please email me.
Best regards,
Jamie
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To add to the message from Frederic above, the National High Magnetic Field lab, is free of charge if you intend to publish your results. We have some of the best NMR instruments in the world.
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Dear all,
we are working on dpp4 inhibitors to target AD. we would like to use sitagliptin as standard. Kindly let us know, on what basis we supposed to select the dose (for rats), as different researchers have used different doses like 10, 30, and 50 mg/kg.
If possible kindly provide me with proper calculation.
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Irrespective on the compound the dose is usually less than 10 mg/Kg. Then I woulg suggest to use 10. If you get not results you may go to 20 but honestly doing to 50 and seeing "somehting" may be just unspecific. Is it possible to use big doses to "cure" disease, sure but better if one finds a compound efficacious at a low dose.
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Hello all,
I was trying to find a anti-Tau antibody to stain neuronal axons of frozen brain slices from healthy mice. However, I learned that hyperphosphorylated Tau is also the hallmark of Alzheimer's disease so it is also used to determine pathological state of Alzheimer's disease (eg. 3x-Tg) mouse tissue.
So I was wondering, is there a distinction between the Tau antibodies used in these two cases? It sounds like Tau has different phosphorylated states in two cases, but which antibody should I use if I just want to stain axons of healthy mouse slices?
Thank you very much for your help on this!
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Thank you very much for your great advice, Aderemi! I really appreciate it.
-Xiao
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If the answer is positive, please describe it. I am looking for any correct answer, please don't hesitate to contact me.
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Thank you dear Susana Rivera-Mancía. Your response was so helpful.
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Non-valvular atrial fibrillation (NVAF) is more common with increasing age. Doctors are increasingly asked about anticoagulation in such patients.
Is it appropriate to give anticoagulation in patients aged ≥ 90 years with NVAF who are:
a. Ambulatory and having preserved cognition.
b. Partially dependent with impaired cognition and brain CT evidence of lacunar infarcts.
c. On Nosogastric (NGT) or PEG tube feeding with associated Alzheimer's disease and bedridden status.
Any evidence-based answers will be appreciated.
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Hi Muhammad,
Thanks for your question, certainly a clinical conundrum encountered increasingly frequently and one for which direct evidence is limited. However, a nice review I read recently summarises this well, particularly the impact that NOAC profiles have on the risk:benefit decision you nicely present:
This article provides a very telling conclusion:
"The literature suggests that elderly adults with AF—even those with high bleeding risk—benefit from anticoagulation. The benefit of anticoagulation appears to be most marked in those with high stroke and bleeding risk, a category into which many elderly adults fall. By reducing the risk of ICH, the DOACs may tip this risk:benefit ratio even further toward anticoagulation."
Hope this helps.
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Does anyone know of online resources which provide a comprehensive list of all genes associated with Alzhemer's disease?
Thanks!
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Hi Loretta,
Visit this website: https://www.alzforum.org/
Go to Database tab and select Alzgene and press SEARCH THE ALZGENE DATABASE .
Good luck!
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For studying anti AZ action of drugs through behavioural studies, in articles training (for memory related behavioural studies) has been given after the induction.
Now my doubt is what is the point of logic in giving the training after inducing alzheimer's and what may be the reason behind to do so.
My intention is training should be given prior to the induction, memory should be tested during induction and treatment period as well.
Kindly clarify me with correct method.
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Training after inducing Alzheimer is to see what possible can counteract it. Cf. our study:
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We have a project using MC65 cells which are a Tet-OFF line for expression of the C99 fragment of APP. Tetracycline withdrawal produces cell death in this line within 2-4 days.
We want to look at ABeta toxicity but ideally want to look at effects from the full length APP protein instead of the C99 fragment.
Does anyone know if there is a stable transfected line out there with full length APP over-expression that can be used for similar toxicity measures?
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Hi,
You might want to consider using the Mouse Neuro2a (N2a) neuroblastoma cells stably overexpressing the human Swedish mutant (K670N, M671L) APP (N2aAPPsw, clone Swe.10). This is available as a gift (I think) from Dr G. Thinakaran (The University of Chicago, IL, USA).
Good luck.
Aderemi.
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Hi,
I am trying to look for basal ERK phosphorylation in N2a cells. Although, I am able to detect very good intensity of bands for total ERK, but the p-ERK bands are hardly visible. Also, when the basal p-ERK is very low in these cells, the extent of effect of stimulation with any agonist or chemical is very minimal.
I have to repeatedly thaw new vials every week to see which batch of cells give decent p-ERK basal levels.
Is this problem faced by other members here? How can one resolve this issue such that the cells maintain good levels of basal ERK phoshphorylation?
Media used: DMEM+ 10% FBS+ Penicillin/ Streptomycin
Antibodies: p-ERK and t-ERK antibodies from Cell Signaling
Looking forward to your helpful suggestions
Apurva
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Hello Agrawal,
I agree Sabine Strehl about isolation of phospho protein issue. And I'd suggest you to
  • increase loading concentraion of your protein
  • add more antibody (1:500 instead of 1:1000 etc.)
  • use more chemiluminescence buffer or adjust waiting time (more or less) in clb.
Also, just for an idea, maybe phosphorylation affect of protein during transfer. So you can try optimize the transfer time. And lastly, if you have materials you can do immunoprecipitation. I hope you can solve problem.
Good luck!
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Geneticists have made risk assessments of developing Alzheimer's by age, gender, and APOE genotype. Christensen et al. (2008), in "Incorporating ethnicity into genetic risk assessment for Alzheimer disease" have further refined the assessment by ethnicity but only between African American and White. Has anyone also incorporated Hispanic/Latino ethnicity into a risk assessment by APOE genotype?
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Hi Etienne!
Here you have many references about studies on ApoE4 in Latin America.
Hope you find it useful!
Best
Josefina
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I am looking for any correct answer, please don't hesitate to contact me.
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Thank you dear Dulce and dear Bobbi, your Answers were so helpful.
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I'm studying learning potential and cognitive plasticity in elder adults with mild cognitive impairment (MCI), and secondly in Parkinson disease, Alzheimer disease, and healthy subjects. If anyone has recent researchs that could help me with this study, I'll be very grateful. 
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Dear Maria,
We recently published a paper addressing the learning potential of older healthy adults in a university context. Our paper covers mean performance across a range of undergraduate courses, and takes a multi-domain approach to investigating predictors of this educational performance. If this sounds of interest, you can find the publication on my RG profile.
Best of luck with your research.
David.
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If I design a peptide for preventing aggregation of Abeta 42 peptide, what are aspects should I consider if I want to suggest it as drug for Alzheimer disease. What all are the properties should that peptide have? What are all the characterizations should I perform?
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Hi there,
I'm sure that there are a lot of possible approaches to screen peptide libraries for peptides that prevent A-beta aggregation in-vitro.
However, in contrast to small molecule inhibitors, the main issue with peptides will be the delivery: It will probably not be easy for your peptides to cross the blood-brain-barrier and get into the central nervous system.
Another important aspect is the in-vivo stability of your peptides. If they are unstable and rapidly degraded in-vivo, they will not be very useful. At the same time, you want to make sure your peptides cannot oligomerize or aggregate.
You will find a bit about analytical methods for the characterization of therapeutic peptides here:
Best,
Sebastian
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Standard use of Confabulation questionnaires may sometimes provoke the production of momentary confabulations among patients (McVittie et al., 2014). Provided that clinicians usually have to rely on their observational abilities to detect single symptoms (e.g. confabulations), can quantitative and qualitative research methods implement for a better assessment ? 
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yes thank you
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Epidemiological and basic science evidence suggests a possible shared pathophysiology between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). It has even been hypothesized that AD might be ‘type 3 diabetes’. The present review summarizes some of the evidence for the possible link, putative biochemical pathways and ongoing clinical trials of anti-diabetic drugs in AD patients.
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A small percentage of people with Alzheimer’s disease (less than 1 percent) have an early-onset type associated with genetic mutations. Individuals who have these genetic mutations are guaranteed to develop the disease. An ongoing clinical trial conducted by the Dominantly Inherited Alzheimer Network (DIAN), is testing whether antibodies to beta-amyloid can reduce the accumulation of beta-amyloid plaque in the brains of people with such genetic mutations and thereby reduce, delay or prevent symptoms. Participants in the trial are receiving antibodies (or placebo) before they develop symptoms, and the development of beta-amyloid plaques is being monitored by brain scans and other tests.
Another clinical trial, known as the A4 trial (Anti-Amyloid Treatment in Asymptomatic Alzheimer’s), is testing whether antibodies to beta-amyloid can reduce the risk of Alzheimer’s disease in older people (ages 65 to 85) at high risk for the disease. The A4 trial is being conducted by the Alzheimer’s Disease Cooperative Study.
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Hello every body,
i am going to investigate "the effect of X substance on cell fate (cell death mechanism) in Alzheimeric cell" but im not sure about select of suitable cell line. Please guide me in this area.
Thanks in advance!
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Hi
You can try with SK N SH Neuroblastoma cells.