Miyako Taniguchi's research while affiliated with Tottori University and other places
Background/objectives This study assessed the effect of continuous ingestion of monosodium l-glutamate (MSG) on cognitive function and dietary score in dementia patients. Subjects/methods This was a single-blind, placebo-controlled trial involving 159 subjects with dementia residing in a hospital or nursing home. We assigned the subjects to a group that ingested MSG thrice daily (0.9 g/dose) (MSG group; n = 79) or a group that ingested NaCl thrice daily (0.26 g/dose) (Control group; n = 80). This study consisted of a 12-week intake period, followed by a 4-week follow-up period without the ingestion of MSG or NaCl. We performed physical examination, cognitive symptom tests (the Touch Panel-type Dementia Assessment Scale (TDAS) and Gottfries–Bråne–Steen Scale (GBSS)), palatability and behaviour questionnaires, and blood tests before and after the intervention and after the follow-up period. Results There were no significant differences in the TDAS and GBSS total scores between the groups before and after the intervention. However, regarding the TDAS sub-items, “the accuracy of the order of a process” did not deteriorate in the MSG group compared with that observed in the Control group (p < 0.05). At the follow-up assessment, the TDAS total scores in the MSG group showed significant improvement compared with those reported in the Control group (p < 0.05). Furthermore, there was a correlation of changes from pre-intervention to post-intervention between the TDAS and enjoyment of the meal (r = −0.299, p = 0.049). Conclusions Our results suggest that continued ingestion of MSG has an effect on cognitive function. Furthermore, the patients with improved questionnaires about palatability survey showed greater improvement in cognitive function.
The aim of this study was to test the diagnostic value of cerebrospinal fluid (CSF) beta-amyloid (Aβ1-42), phosphorylated tau, and total tau (tau) to discriminate Alzheimer's disease (AD) dementia from other forms of dementia. A total of 675 CSF samples collected at eight memory clinics were obtained from healthy controls, AD dementia, subjective memory impairment, mild cognitive impairment, vascular dementia, Lewy body dementia (LBD), fronto-temporal dementia (FTD), depression, or other neurological diseases. CSF Aβ1-42 showed the best diagnostic accuracy among the CSF biomarkers. At a sensitivity of 85%, the specificity to differentiate AD dementia against other diagnoses ranged from 42% (for LBD, 95% confidence interval or CI = 32-62) to 77% (for FTD, 95% CI = 62-90). CSF Aβ1-42 discriminates AD dementia from FTD, but shows significant overlap with other non-AD forms of dementia, possibly reflecting the underlying mixed pathologies. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Dementia is a declined state of cognitive functions which impair daily and social life mainly caused by progressive neurodegenerative disease, such as Alzheimer's disease(AD). The present study showed that about 15% of patients in Japan aged over 65 have dementia. The important point regarding the diagnosis of dementia is to detect it as early as possible. It is critical for the diagnosis to measure the indicators in blood and cerebrospinal fluid (CSF). Blood tests are useful to eliminate other factors that lead to cognitive decline derived from physical causes. CSF markers are significant for monitoring the existence and progression of neuropathologies. We need to accumulate extensive knowledge of the features, types, pathologies, development, and progress of dementia in order to assess patients and/or measured values.
To examine whether the diagnosis method of neuronal dysfunction (DIMENSION), a new electroencephalogram (EEG) analysis method, reflected pathological changes in the early stages of Alzheimer's disease (AD), we conducted a comparative study of cerebrospinal fluid markers and single-photon emission computed tomography. Subjects cincluded 32 patients in the early stages of AD with a Mini-Mental State Examination score ≥24 (14 men, 18 women; mean age, 77.3 ± 9.2 years). Cerebrospinal fluid samples were collected from AD patients, and cerebrospinal fluid levels of phosphorylated tau protein (p-tau) 181 and amyloid β (Aβ) 42 were measured with sandwich ELISA. EEG recordings were performed for 5 min with the subjects awake in a resting state with their eyes closed. Then, the mean value of the EEG alpha dipolarity (Dα) and the standard deviation of the EEG alpha dipolarity (Dσ) were calculated with DIMENSION. Single-photon emission computed tomography analyses were also performed for comparison with DIMENSION measures. Patients with parietal hypoperfusion had significantly increasing p-tau181, decreasing Dα, and increasing Dσ. In addition, there was a negative correlation between Dα and p-tau181, p-tau181/Aβ42, and a positive correlation between Dσ and p-tau181/Aβ42. Dα and Dσ were related to cerebral hypoperfusion and p-tau181/Aβ42. DIMENSION was able to detect changes in the early-stage Alzheimer's brain, suggesting that it is possibility as a useful examination for early-stage AD with a difficult discrimination in clinical conditions. Moreover, EEG measurement is a quick and easy diagnostic test and is useful for repeated examinations.
Figure S1. Difference between male and female subjects for p3-Alcαand Aβ40 levels. Subjects in respective cohorts are analyzed for p3-Alcα and Aβ40 levels in different gender. F, female subjects; M, male subjects. Bars indicate average. No significance, using the Dunn's multiple comparisons test following the Kruskal-Wallis test, was detected for p3-Alcα and Aβ40 levels between male and female subjects in respective CDR and OND.
Alcadeinα (Alcα) is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-β precursor protein (APP). Successive cleavage of APP by β- and γ-secretases generates the aggregatable amyloid-β peptide (Aβ), while cleavage of APP or Alcα by α- and γ-secretases generates non-aggregatable p3 or p3-Alcα peptides. Aβ and p3-Alcα can be recovered from human cerebrospinal fluid (CSF). We have previously reported alternative processing of APP and Alcα in the CSF of some patients with sporadic mild cognitive impairment (MCI) and AD (SAD). Using the sandwich enzyme-linked immunosorbent assay (ELISA) system that detects total p3-Alcα, we determined levels of total p3-Alcα in CSF from subjects in one of four diagnostic categories (elderly controls, MCI, SAD, or other neurological disease) derived from three independent cohorts. Levels of Aβ40 correlated with levels of total p3-Alcα in all cohorts. We confirm that Aβ40 is the most abundant Aβ species, and we propose a model in which CSF p3-Alcα can serve as a either (1) a nonaggregatable surrogate marker for γ-secretase activity; (2) as a marker for clearance of transmembrane domain peptides derived from integral protein catabolism; or (3) both. We propose the specification of an MCI/SAD endophenotype characterized by co-elevation of levels of both CSF p3-Alcα and Aβ40, and we propose that subjects in this category might be especially responsive to therapeutics aimed at modulation of γ-secretase function and/or transmembrane domain peptide clearance. These peptides may also be used to monitor the efficacy of therapeutics that target these steps in Aβ metabolism.
Table S1. Details of individual subjects in Cohort 1 (Japanese cohort) Table S2. Details of individual subjects in Cohort 2 (US cohort) Table S3. Details of individual subjects in Cohort 3 (Japanese cohort) Table S4. Details of individual subjects in Cohort 4 (Australian cohort).
Figure S2. Difference between ApoE4 carriers and non-carriers for p3-Alcaand Aβ40 levels of cohort 3. ApoE4 carriers (+) and non-carriers (-) are compared for p3-Alca and Aβ40 levels. Nosignificance, using the Dunn's multiple comparisons test following the Kruskal-Wallis test, was detected for p3-Alca and Aβ40 levels between ApoE4 carriers and non-carriers.
Alzheimer's disease (AD) is one of the most significant diseases associated with ageing. As the disease progresses, symptoms including olfactory dysfunction often appear along with cognitive dysfunction. We examined olfactory and other indexes to investigate correlations between them and the validity of an olfactory test for screening for AD. To assess whether odorant identification will be a useful diagnostic tool, we investigated the olfactory ability of Alzheimer's disease patients (ADs) using the Odor Stick Identification Test for the Japanese. As a control, we compared ADs to aged people without AD or dementia. To investigate the relationship between olfactory loss and severity of AD, we used the Mini-Mental State Examination, Alzheimer's Disease Assessment Scale, biomarkers in spinal fluid and single-photon emission computed tomography as brain imaging. In comparing the controls and ADs, we believe that there are significant differences, with ADs having particularly low activity with regard to olfactory function and some odorants. We showed that there was a definite correlation between cognitive and olfactory function. To confirm this, we sorted subjects by markers of severity scores for comparison. In all areas, the AD group had more serious olfactory dysfunction, including in the early stages of AD. This study suggests that olfactory tests such as the Odor Stick Identification Test for the Japanese can be useful for assessing severity of AD, including cognitive dysfunction. Further investigations will enable us to establish an olfactory assessment method for the screening or diagnosis of AD.
Objective:The most common pathogenesis for familial Alzheimer's disease (FAD) involves misprocessing (or alternative processing) of the amyloid precursor protein (APP) by γ-secretase due to mutations of the presenilin 1 (PS1) gene. This misprocessing/alternative processing leads to an increase in the ratio of the level of a minor γ-secretase reaction product (Aβ42) to that of the major reaction product (Aβ40). Although no PS1 mutations are present, altered Aβ42/40 ratios are also observed in sporadic Alzheimer's disease (SAD), and these altered ratios apparently reflect deposition of Aβ42 as amyloid.Methods:Using immunoprecipitation-mass spectrometry with quantitative accuracy, we analyzed in the cerebrospinal fluid (CSF) of various clinical populations the peptide products generated by processing of not only APP but also an unrelated protein, alcadein (Alc). Alc undergoes metabolism by the identical APP α-secretases and γ-secretases, yielding a fragment that we have named p3-Alcα because of the parallel genesis of p3-Alcα peptides and the p3 fragment of APP. As with Aβ, both major and minor p3-Alcαs are generated. We studied the alternative processing of p3-Alcα in various clinical populations.Results:We previously reported that changes in the Aβ42/40 ratio showed covariance in a linear relationship with the levels of p3-Alcα [minor/major] ratio in media conditioned by cells expressing FAD-linked PS1 mutants. Here we studied the speciation of p3-Alcα in the CSF from 3 groups of human subjects (n = 158): elderly nondemented control subjects; mild cognitive impairment (MCI) subjects with a clinical dementia rating (CDR) of 0.5; SAD subjects with CDR of 1.0; and other neurological disease (OND) control subjects. The CSF minor p3-Alcα variant, p3-Alcα38, was elevated (p < 0.05) in MCI subjects or SAD subjects, depending upon whether the data were pooled and analyzed as a single cohort or analyzed individually as 3 separate cohorts.Interpretation:These results suggest that some SAD may involve alternative processing of multiple γ-secretase substrates, raising the possibility that the molecular pathogenesis of SAD might involve γ-secretase dysfunction. Ann Neurol 2011;69:1026–1031
The most common pathogenesis for familial Alzheimer's disease (FAD) involves misprocessing (or alternative processing) of the amyloid precursor protein (APP) by γ-secretase due to mutations of the presenilin 1 (PS1) gene. This misprocessing/alternative processing leads to an increase in the ratio of the level of a minor γ-secretase reaction product (Aβ42) to that of the major reaction product (Aβ40). Although no PS1 mutations are present, altered Aβ42/40 ratios are also observed in sporadic Alzheimer's disease (SAD), and these altered ratios apparently reflect deposition of Aβ42 as amyloid. Using immunoprecipitation-mass spectrometry with quantitative accuracy, we analyzed in the cerebrospinal fluid (CSF) of various clinical populations the peptide products generated by processing of not only APP but also an unrelated protein, alcadein (Alc). Alc undergoes metabolism by the identical APP α-secretases and γ-secretases, yielding a fragment that we have named p3-Alc(α) because of the parallel genesis of p3-Alc(α) peptides and the p3 fragment of APP. As with Aβ, both major and minor p3-Alc(α) s are generated. We studied the alternative processing of p3-Alc(α) in various clinical populations. We previously reported that changes in the Aβ42/40 ratio showed covariance in a linear relationship with the levels of p3-Alc(α) [minor/major] ratio in media conditioned by cells expressing FAD-linked PS1 mutants. Here we studied the speciation of p3-Alc(α) in the CSF from 3 groups of human subjects (n = 158): elderly nondemented control subjects; mild cognitive impairment (MCI) subjects with a clinical dementia rating (CDR) of 0.5; SAD subjects with CDR of 1.0; and other neurological disease (OND) control subjects. The CSF minor p3-Alc(α) variant, p3-Alc(α) 38, was elevated (p < 0.05) in MCI subjects or SAD subjects, depending upon whether the data were pooled and analyzed as a single cohort or analyzed individually as 3 separate cohorts. These results suggest that some SAD may involve alternative processing of multiple γ-secretase substrates, raising the possibility that the molecular pathogenesis of SAD might involve γ-secretase dysfunction.
The Alzheimer's Disease Assessment Scale (ADAS) was designed as a rating scale for the severity of dysfunction in the cognitive and non-cognitive behaviours that are characteristic of persons with Alzheimer's disease. Its subscale, the ADAS-cog, is a cognitive testing instrument most widely used to measure the impact of the disease. However, the ADAS-cog takes more than 45 min to administer and requires a qualified clinical psychologist as the rater. A more comprehensive rating battery is therefore required. In the present study, we developed a computerized test battery named the Touch Panel-type Dementia Assessment Scale (TDAS), which was intended to substitute for the ADAS-Cog, and was specifically designed to rate cognitive dysfunction quickly and without the need of a specialist rater. The hardware for the TDAS comprises a 14-inch touch panel display and computer devices built into one case. The TDAS runs on Windows OS and was bundled with a custom program made with reference to the ADAS-cog. Participants in the present study were 34 patients with Alzheimer's disease. Each participant was administered the ADAS-cog and the TDAS. The test scores for each patient were compared to determine whether the severity of cognitive dysfunction of the patients could be rated equally as well by both tests. Pearson's correlation coefficient showed a significant correlation between the total scores (r= 0.69, P < 0.01) on the two scales for each patient. The Kendall coefficients of concordance obtained for the three corresponding pairs of tasks (word recognition, orientation, and naming object and fingers) showed the three TDAS tasks can rate symptoms of cognitive decline equally as well as the corresponding items on the ADAS-cog. The TDAS appears to be a sensitive and comprehensive assessment battery for rating the symptoms of Alzheimer's disease, and can be substituted for the ADAS-cog.
It is often difficult to diagnose disease in elderly patients, in particular those with dementia, who do not present with typical symptoms. This report describes our experience of an elderly patient (an 83-year-old woman) who presented with a chief complaint of memory loss, showed a marked inflammatory response, and was diagnosed with large-vessel giant cell arteritis (GCA) on the basis of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) findings. She had no symptoms typical of GCA including jaw claudication, visual field defect and heavy headed feeling. Corticosteroid therapy resulted in a trend toward improvement in the inflammatory response and then she first recognized that she might have experienced slight dull headache before treatment of GCA. This was probably because this patient had large-vessel GCA, which produces a few symptoms in the head and neck, and because she had Alzheimer's disease and could not accurately describe her symptoms. Our experience suggests the usefulness of FDG-PET for the diagnosis of GCA, particularly in elderly patients without typical symptoms.
Recently, the importance of non-pharmacological therapies for dementia has come to the fore. In the present study, we examined the curative effects of aromatherapy in dementia in 28 elderly people, 17 of whom had Alzheimer's disease (AD). After a control period of 28 days, aromatherapy was performed over the following 28 days, with a wash out period of another 28 days. Aromatherapy consisted of the use of rosemary and lemon essential oils in the morning, and lavender and orange in the evening. To determine the effects of aromatherapy, patients were evaluated using the Japanese version of the Gottfries, Brane, Steen scale (GBSS-J), Functional Assessment Staging of Alzheimer's disease (FAST), a revised version of Hasegawa's Dementia Scale (HDS-R), and the Touch Panel-type Dementia Assessment Scale (TDAS) four times: before the control period, after the control period, after aromatherapy, and after the washout period. All patients showed significant improvement in personal orientation related to cognitive function on both the GBSS-J and TDAS after therapy. In particular, patients with AD showed significant improvement in total TDAS scores. Result of routine laboratory tests showed no significant changes, suggesting that there were no side-effects associated with the use of aromatherapy. Results from Zarit's score showed no significant changes, suggesting that caregivers had no effect on the improved patient scores seen in the other tests. In conclusion, we found aromatherapy an efficacious non-pharmacological therapy for dementia. Aromatherapy may have some potential for improving cognitive function, especially in AD patients.
Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins, designated Alc(alpha), Alc(beta), and Alc(gamma). The Alcs express in neurons dominantly and largely colocalize with the Alzheimer amyloid precursor protein (APP) in the brain. Alcs and APP show an identical function as a cargo receptor of kinesin-1. Moreover, proteolytic processing of Alc proteins appears highly similar to that of APP. We found that APP alpha-secretases ADAM 10 and ADAM 17 primarily cleave Alc proteins and trigger the subsequent secondary intramembranous cleavage of Alc C-terminal fragments by a presenilin-dependent gamma-secretase complex, thereby generating "APP p3-like" and non-aggregative Alc peptides (p3-Alcs). We determined the complete amino acid sequence of p3-Alc(alpha), p3-Alc(beta), and p3-Alc(gamma), whose major species comprise 35, 37, and 31 amino acids, respectively, in human cerebrospinal fluid. We demonstrate here that variant p3-Alc C termini are modulated by FAD-linked presenilin 1 mutations increasing minor beta-amyloid species Abeta42, and these mutations alter the level of minor p3-Alc species. However, the magnitudes of C-terminal alteration of p3-Alc(alpha), p3-Alc(beta), and p3-Alc(gamma) were not equivalent, suggesting that one type of gamma-secretase dysfunction does not appear in the phenotype equivalently in the cleavage of type I membrane proteins. Because these C-terminal alterations are detectable in human cerebrospinal fluid, the use of a substrate panel, including Alcs and APP, may be effective to detect gamma-secretase dysfunction in the prepathogenic state of Alzheimer disease subjects.
To evaluate the capability of a computerized test battery for Alzheimer's disease screening which has been newly developed to provide a standardized and efficient method for widespread use in routine clinical and community-based settings. Participants were 72 individuals diagnosed with Alzheimer's disease and 102 healthy elderly individuals. Both groups were tested by the battery. Receiver operating characteristic analysis was used to examine the ability of the battery to differentiate between those with Alzheimer's disease and cognitively healthy elderly individuals. On a group level, the Alzheimer's disease group performed worse than the control group on each of the 4 computerized test tasks. Receiver operating characteristic analysis yielded maximum sensitivity and specificity values of 96% and 86% for total scores, respectively. We believe the battery is very useful for routine clinical and community-based settings.
We have developed a computerized testing system for screening dementia in community-based settings. The system was assembled with a touch-panel display and computer devices unified into one case. This made the hardware a very compact, light and easy to carry unit. Two test programs were implemented in the system, one for primary screening and the other for close examination. The primary screening program, which was intended to screen persons who are suspected of having dementia in community-based settings, consisted of 4 test tasks. The close examination program was designed to diagnose the dementia and was composed of 10 test tasks. Throughout the whole process, users were guided not only by text prompts but also by voice instructions. In the test process, the system presents questions by text, figures and/or voice. Then the system shows the choice icons on the computer display and requires the subject to touch the correct icon. By this method, even aged persons could easily operate the system. Results f the primary screening program yielded maximum sensitivity and specificity values of 96% and 86% for the total score, respectively. By applying this system to community-based settings, we have detected 55 persons as mild cognitive impairment (MCI) and 74 persons as suspicious of suffering from dementia out of 998 elderly residents.
Alzheimer's disease (AD) is a well-known type of dementia. However, it remains difficult to identify AD in the early stage and to distinguish it from other dementing disorders. We examined glycoproteins in cerebrospinal fluid (CSF) as potential biological markers of AD. CSF samples were collected from AD, other dementia and nondemented patients. Glycoproteins in CSF were detected by lectin blotting using wheat germ agglutinin (WGA), and sugar chain analysis was performed by isoelectric focusing. In Alzheimer's CSF, several glycoproteins had lower WGA-binding activities, one of which was sufficiently sensitive and specific to distinguish AD from nondemented controls and other dementias. Further analysis identified this glycosylated protein as transferrin, and altered sugar chain composition of transferrin isoforms was observed despite normal protein levels in CSF. The decreased WGA-binding activity of transferrin in AD is probably due to altered glycosylation of transferrin molecules. Transferrin glycosylation is thus a potential biological marker for AD diagnosis, and changes in this glycosylation may play an important role in the pathophysiology of AD.
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. It is characterized pathologically by the formation of senile plaques and neurofibrilly tangles in the brain. Diagnostic markers for detecting earlier stages of AD are needed. We measured the intensity of concanavalin A (Con A) binding activities of glycoproteins of the cerebrospinal fluid (CSF) and serum of subjects to clarify the modification of core mannose since we expected that aberrant glycosylation of glycoproteins might be useful as a new biomarker for detecting AD. CSF samples were collected from 15 patients with probable AD (AD group), 5 patients with probable dementia with Lewy bodies (DLB) (DLB group) and 8 controls without dementia (control group), whereas serum samples from 20 patients with probable AD and 20 controls without dementia were also collected. Glycoproteins in the CSF and serum were detected by lectin blotting using Con A. In the CSF of the AD group, 2 Con A binding glycoproteins were significantly higher compared with the control group. Furthermore, using analysis of variance, 3 Con A binding glycoproteins detected from the CSF of the AD group showed significant differences among the 3 groups. The levels of 3 Con A binding glycoproteins were significantly lower than in non-dementia controls in the serum. These changes in Con A binding activities did not depend on the amount of proteins. Therefore, the data indicate that the aberrance of protein glycosylation relates to the pathology of AD, and has some promise as a new biomarker for the diagnosis of AD.
In recent years, Alzheimer's disease (AD) has increased in incidence in Japan and elsewhere, and the marketing of donepezil hydrochloride (Aricept®) has allowed for the treatment of AD. These circumstances have encouraged the development of and research in markers for the early diagnosis of AD. Currently, the measurement of phosphorylated tau protein in the cerebrospinal fluid is considered to provide the most reliable and useful diagnostic marker for AD. For this purpose, a screening test using a touch panel computer can be recommended. The results of our study also suggest that the analysis of acetylcholine receptor α7 genetic polymorphism may be useful as a marker in the treatment with acetylcholine esterase inhibitors.
Background: Mild cognitive impairment (MCI) refers to the clinical condition between normal aging and Alzheimer's disease (AD) and has a high probability of developing into AD. Early detection of MCI is important because early detection and appropriate follow-up treatment can prevent the disease from progressing. Therefore, MCI is an important candidate for screening and possible intervention.Methods: We have developed a computerized screening test system to identify cognitive decline. This system consists of six tests (age and year-of-birth validity test, three-word memory test, time orientation test, first modified delayed-recall test, visual working memory test and second modified delayed-recall test). The scores obtained from three groups (MCI patients, AD patients and healthy control subjects) were analyzed to evaluate the sensitivity and specificity required for the screening of MCI.Results: The system was well accepted by the patients. All of the test procedures were completed within 5 min. Significant group differences in all test results were found. The system has sensitivity and specificity values of 82% and 87%, respectively, when used as a screen for MCI.Conclusion: The system is useful for the screening of cognitive disorders.
... When the lavender massage and the placebo massage results were compared, it shows that aromatherapy or lavender massage was more effective in reducing dysmenorrhea (Apay, Arslan, Akpinar, & Celebioglu, 2012). Jimbo et al. (2009) studied the effect of aromatherapy on Alzheimer"s patients in Japan. Dementia is one of the common symptoms suffered by Alzheimer"s patients. ...
... γ-secretase is mainly involved in intramembranous proteolysis of type I membrane proteins. It cleaves numerous functionally important proteins, such as APP (De Strooper et al., 1998), Notch (De), E-cadherin (Marambaud et al., 2002), ErbB4 (Ni et al., 2001), CD44 (Lammich et al., 2002), tyrosinase (Wang et al., 2006), TREM2 (Wunderlich et al., 2013) and Alcadein (Hata et al., 2012) among others, suggesting the participation of γ-secretase in a vast range of biological activities (Haapasalo and Kovacs, 2011). The best-studied γ-secretase substrates are APP for its roles in AD, and Notch for its importance in development and cell fate determination (Kopan and Ilagan, 2009; Andersson et al., 2011). ...
... Most such tests are self-administered thus reducing even further the need for personnel and enabling older adults to self-monitor their cognitive health (). Experimental tests and batteries featuring an administration time of less than 5 minutes take this trend even further allowing for screening on a massive scale (Inoue, Jinbo, Nakamura, Taniguchi, & Urakami, 2009), (). There is currently a wealth of research activity on computerized testing ranging from the evaluation of existing tests and batteries to the design of new ones. ...
... AD diagnosis is based mainly on clinical examination and neu- ropsychological testing, such as Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and evaluation of clinical dementia rate (CDR). In addition, in several centers it is sup- ported by positron emission tomography (PET-amyloid, PET-tau, fluorodeoxyglucose-PET (FDG-PET)), magnetic resonance imaging (MRI) as well as by biochemical analysis of cerebrospinal fluid (CSF) for the levels of total and hyperphosphorylated tau protein and for the amounts of Aβ42 and Aβ40 peptides (Brier et al., 2016;Ewers et al., 2015;Villemagne, 2016;Wei et al., 2016a;Zimmer et al., 2014). ...
... The GS-dependent product p3-Alc has been proposed as a biomarker for sporadic AD cases , since its plasma levels are enhanced in cohorts of clinically diagnosed AD patients or in patients with concomitant decrease in the Mini- Mental State Examination score, when compared with age-matched non-demented subjects . In addition, p3-Alc levels are also increased in the cerebrospinal fluid of patients with mild cognitive impairment or with clinical dementia . ...
... Previously, glycosylation-based biomarker studies relied on lectin staining or 2D gel electrophoresis approaches to measure the total glycosylation changes or the total glycoprotein changes, which suffer from low-throughput, limited sensitivity, and limited site- specific glycosylation information [180,181]. With the advance- ment of glycoproteomics methodologies, glycosylation level changes can be pinpointed on a specific site and further micro- heterogeneity differences can be revealed through intact glyco- peptide analysis in a high-throughput manner. ...
... Elevated Ab levels further correlate with anxiety-like behavior (Lee et al., 2004; Porter et al., 2003) or atypical olfactory-behavior (Alvarado-Martinez et al., 2013; Cheng et al., 2013; Wesson et al., 2010). These pathological phenotypes represent also relevant criteria for the early diagnosis of neuropathology, such as AD or Parkinson's disease (PD) (Baba et al., 2012; Berendse and Ponsen, 2006; Jimbo et al., 2011). To date, only anxiolytic effects of DMSO have been reported (Matheus et al., 1997) but effects on memory have not been studied. ...
... Although different cognitive tests have different designs, most of the computerized and paper-and-pencil cognitive tests contain a memory test, such as 3-word recall test in the Mini-Mental State Examination 11 and 3-word recall test in a computerized test battery MPS-1000. 12 Some memory tests are solely verbal or visual memory tests, such as the Hopkins Verbal Learning Test 13 and Rey Complex Figure. 14 Some studies showed that verbal and visual memory tests are sensitive for MCI and dementia screening, 15e18 because deterioration of the ability to learn and remember new in- formation is one of the earliest signs and symptoms for MCI and Alzheimer disease. ...
... The Touch Panel-type Dementia Assessment Scale (TDAS) was used for cognitive assessment . It was developed by modifying the Alzheimer's Disease Assessment Scale- cognitive subscale (ADAS-cog) , a scale to assess AD patients' cognitive function, and by equipping it with a touch panel system that enabled us to conduct a test in a shorter period of time (shortened from 60 to 20 min) even without expert assistance. ...
... Plasma proteins of amyloid pathology, circulatory miRNAs, cytokines, kinases, axonal proteins, lipids, and fragments of already known AD markers are currently investigated for their potential as blood- based AD biomarker ( Lista et al., 2013;Huynh and Mohan, 2017). In addition, serum TF level ( Squitti et al., 2010), desaturation level of serum TF-iron ( Hare et al., 2015), glycosylated-TF in CSF ( Guevara et al., 1998;Van Rensburg et al., 2000;Taniguchi et al., 2008;Shirotani et al., 2011) and serum ( Yu et al., 2003) has been proposed as potential AD biomarkers. The present study has shown that the total TF level in the CSF of postmortem AD patients decreased compared to age-matched control but the serum TF level remained unaltered which makes total TF level unsuitable as a diagnostic biomarker. ...