Neurodegenerative Diseases Journal Impact Factor & Information

Publisher: Karger

Journal description

Neurodegenerative Diseases is a bimonthly, multidisciplinary journal for the publication of advances in the understanding of neurodegenerative diseases, including Alzheimer disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington disease and related neurological and psychiatric disorders. Neurodegenerative Diseases publishes results from basic and clinical scientific research programs designed to better understand the normal functions of genes and proteins involved in neurodegenerative diseases, to characterize their role in pathogenic disease mechanisms, to model their functions in animals and to explore their roles in the diagnosis, treatment and prevention of neurodegenerative diseases. It is our firm belief that successful strategies for novel treatments of neurodegenerative diseases will emerge from the intelligent integration of basic neurobiology with clinical sciences. Therefore, Neurodegenerative Diseases will accept high-quality papers from a broad spectrum of scientific research areas ranging from molecular and cell biology to neuroscience, pharmacology, genetics and the clinical sciences.

Current impact factor: 3.51

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.511
2013 Impact Factor 3.454
2012 Impact Factor 3.41
2011 Impact Factor 3.056
2010 Impact Factor 3.791
2009 Impact Factor 3.496
2008 Impact Factor 2.989

Impact factor over time

Impact factor

Additional details

5-year impact 3.12
Cited half-life 4.00
Immediacy index 0.80
Eigenfactor 0.00
Article influence 0.92
Website Neurodegenerative Diseases website
Other titles Neuro-degenerative diseases
ISSN 1660-2862
OCLC 260107464
Material type Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • On author's server or institutional server
    • Server must be non-commercial
    • Publisher's version/PDF cannot be used
    • Publisher copyright and source must be acknowledged
    • Must link to publisher version
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aberrant accumulation of protein aggregates is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Although a buildup of protein aggregates frequently leads to cell death, whether it is the key pathogenic factor in driving neurodegenerative disease remains controversial. HDAC6, a cytosolic ubiquitin-binding deacetylase, has emerged as an important regulator of ubiquitin-dependent quality control autophagy, a lysosome-dependent degradative system responsible for the disposal of misfolded protein aggregates and damaged organelles. Here, we show that in cell models HDAC6 plays a protective role against multiple disease-associated and aggregation-prone cytosolic proteins by facilitating their degradation. We further show that HDAC6 is required for efficient localization of lysosomes to protein aggregates, indicating that lysosome targeting to autophagic substrates is regulated. Supporting a critical role of HDAC6 in protein aggregate disposal in vivo, genetic ablation of HDAC6 in a transgenic SOD1G93A mouse, a model of ALS, leads to dramatic accumulation of ubiquitinated SOD1G93A protein aggregates. Surprisingly, despite a robust buildup of SOD1G93A aggregates, deletion of HDAC6 only moderately modified the motor phenotypes. These findings indicate that SOD1G93A aggregation is not the only determining factor to drive neurodegeneration in ALS, and that HDAC6 likely modulates neurodegeneration through additional mechanisms beyond protein aggregate clearance.
    Neurodegenerative Diseases 09/2015; DOI:10.1159/000437208
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    ABSTRACT: Leukoaraiosis (LA) patients may suffer from sensorimotor dysfunctions. The relationship between behavioral disturbances and changes in the sensorimotor network (SMN) has not been thoroughly elucidated. This study investigated the hypothesized breakdown of communication of SMN and its behavioral consequences in LA. Fluid-attenuated inversion recovery (FLAIR) images, resting-state functional magnetic resonance images (fMRI) and behavioral data were collected from 30 LA patients and 26 healthy individuals (normal controls, NC). The subjects were grouped according to LA severity, as indicated by their FLAIR images. Group independent component analysis was applied to the fMRI data to map the functional connectivity of SMN for NC and LA patients. A whole-brain, voxel-wise analysis was employed to investigate the functional connectivity alteration of SMN in LA. The relationships between LA severity, functional connectivity alteration of the SMN and behavioral clinical symptoms were examined by correlation analysis. The right cingulate motor area (rCMA), left posterior insula and left ventral premotor area showed attenuated functional connectivity in the LA patients. The extent of the attenuation was related to the severity of the disease. Furthermore, the attenuation in the rCMA was associated with worse sensorimotor integration performance. These results suggest that LA impairs sensorimotor integration by interfering with the communication or coordination of these aforementioned regions related to the SMN. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 08/2015; DOI:10.1159/000435918
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    ABSTRACT: Neurodegenerative diseases include a significant number of pathologies affecting the nervous system. Generally, the primary cause of each disease is specific; however, recently, it was shown that they may be correlated at molecular level. This aspect, together with the exhibition of similar symptoms, renders the diagnosis of these disorders difficult. Amyotrophic lateral sclerosis is one of these pathologies. Herein, we report several cases of amyotrophic lateral sclerosis misdiagnosed as a consequence of features that are common to several neurodegenerative diseases, such as Parkinson's, Huntington's and Alzheimer's disease, spinal muscular atrophy, progressive bulbar palsy, spastic paraplegia and frontotemporal dementia, and mostly with the lysosomal storage disorder GM2 gangliosidosis. Overall reports highlight that the differential diagnosis for amyotrophic lateral sclerosis should include correlated mechanisms. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; DOI:10.1159/000435917
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    ABSTRACT: Glucocerebrosidase (GBA) mutations have been described as the most prevalent in Parkinson's disease (PD) and in Lewy body dementia, accounting for up to 7 and 13.8% of cases, respectively. To elucidate the pathophysiology of idiopathic Parkinson's disease (iPD), the pathogenic mechanisms leading to Lewy body accumulation in GBA-associated parkinsonism (GBA-PD) are a matter of current research. However, only few imaging studies, conducted on small GBA-PD patient cohorts, exist. We provide an overview of current structural and functional imaging studies in patients with Gaucher's disease and parkinsonism and in GBA-PD patients, underlining the main differences compared to iPD. A limited number of PET studies have been conducted in GBA-PD, exploring brain metabolism and dopaminergic presynaptic and postsynaptic function. Moreover, structural MRI and spectroscopy studies recently evidenced the differences with iPD, aiding to understand of some peculiar aspects of iPD. Finally, new evidence from transcranial sonography confirms the technique's role in the study of GBA-PD and highlights the additional involvement of the raphe nucleus. Further imaging studies conducted in a broader population of early GBA-PD are warranted to characterize the disease and elucidate the pathophysiological mechanisms underlying GBA-PD and to understand GBA implications in iPD. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; 15(5). DOI:10.1159/000433438
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    ABSTRACT: Previous studies indicate that patients with the parkinsonian subtype of multiple system atrophy (MSA-P) experience cognitive impairment. This study aimed to identify the existence of cognitive impairments and the different topographic patterns of morphological changes in MSA-P by means of imaging analysis, and also whether these morphological changes could be associated with cognitive dysfunctions in MSA-P. We recruited 15 nondemented probable MSA-P patients and 32 normal controls (NC) for neuropsychological testing and MRI. We analyzed morphological changes using cortical thickness analysis, voxel-based morphometry (VBM) and cerebellar volumetry. Multiple linear regression analysis was performed to evaluate the correlation of each cognitive score with the mean thickness of significant cortical-thinning clusters, mean gray-matter density of VBM clusters and cerebellar volume. The scores on the Digit Span Test, the Seoul Verbal Learning Test (immediate and delayed), the phonemic Controlled Oral Word Association Test and the Stroop color test were significantly lower in the MSA-P group than in the NC group. We found two clusters exhibiting significant cortical thinning in the right paracentral lobule and parahippocampal gyrus. VBM analysis revealed significant gray-matter atrophy in the MSA-P group in the bilateral basal ganglia, cerebellum and temporal and frontal cortical areas. Multiple linear regression analysis demonstrated that cognitive dysfunction correlated significantly with thinning in the neocortex, cerebellum and striatum. Our data demonstrate that cortical and cerebellar atrophy and striatal degeneration are associated with cognitive impairment in patients with MSA-P. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; 15(5). DOI:10.1159/000430953
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    ABSTRACT: Alzheimer's disease (AD) is the most common disease causing neurodegeneration. The lower concentration of β-amyloid 1-42 (Aβ1-42) together with increased levels of total tau protein (T-tau) and phosphorylated tau protein (P-tau) in the cerebrospinal fluid (CSF) make a panel of well-established biomarkers in AD diagnosis. Addition of novel biomarkers to the gold standard biomarker panel might improve the diagnostic accuracy of neurodegeneration. This goal might be reached by the use of multiplexing, which is a simultaneous measurement of multiple analytes in a single sample volume and within a single cycle or run. Therefore the aim of the current review was to present, according to our best knowledge, available data concerning the evaluation of concentrations and diagnostic accuracy of well-established biomarkers in AD as well as novel biomarkers analyzed with the use of the bead-based technique. Additionally we discuss the utilization of the bead-based technique as compared to the conventional ELISA method. Literature data indicate that the bead-based technique revealed diagnostic sensitivity, specificity and coefficients of variation at the levels similar to ELISA. Moreover, an addition of novel biomarkers (tested by means of the bead-based technique) to the gold standard biomarker panel improved the diagnostic accuracy of neurodegeneration. Review of literature data shows that the combined analysis of classical CSF biomarkers with novel biomarkers might increase the specificity and sensitivity of performed tests. However, we concluded that the replacement of conventional ELISA with the bead-based technique requires new reference intervals for Aβ1-42, T-tau and P-tau concentrations. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; 15(5). DOI:10.1159/000433439
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    ABSTRACT: Recent studies have suggested overlapping pathological features among motor neuron, cognitive and neurodegenerative diseases. Secondary analysis of 46 amyotrophic lateral sclerosis (ALS) patient autopsies was performed to independently assess pathological feature prevalence (e.g. percent of patients with any positive finding), degree of severity (e.g. mild, moderate, severe), and 2,200+ potential clinical/neuropathological correlations. The possible impact of gender, onset age, onset type (limb vs. bulbar), riluzole treatment, and severe TDP-43 pathology was assessed within patient subgroups. Assessed features (prevalence, severity) include: lateral corticospinal tract degeneration (89%, moderate); Purkinje cell loss (85%, mild); localized neuronal loss (83%, mild to moderate); TDP-43 inclusions (80%, moderate); Betz cell loss (76%, mild); neurofibrillary tangles (78%, severe); anterior corticospinal tract degeneration (72%, moderate); spinal ventral root atrophy (65%, moderate); atherosclerosis (35%, mild); β-amyloid (35%, mild); tauopathy/tau inclusions (17%, mild); ventricular dilation (13%, mild); Lewy body formation (11%, mild); microinfarcts (7%, mild); and α-synuclein (4%, mild). Twenty-two percent of patients met criteria for Alzheimer's disease (AD) and 26% for frontotemporal lobar degeneration. Substantial differences were identified in the AD group and in the different onset age groups. Our findings support the hypothesis that ALS and its variants could comprise a larger neuropathological continuum. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; 15(5). DOI:10.1159/000433581
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    ABSTRACT: Parkin biology has emerged as an exciting area of pharmaceutical development for several human diseases, including cancer and neurodegeneration. Parkin's role is multifaceted in human health and disease and its function affecting major cellular quality control mechanisms, including the ubiquitin-proteasome and autophagy-lysosome systems, is critical in the maintenance of cellular homeostasis. Loss of Parkin function due to aging, protein instability and gene mutations is manifest in a number of human diseases, contributing to the validation of this protein as a therapeutic target. Parkin activation to mobilize cellular quality control mechanisms and counteract dyshomeostasis is a highly desirable area for therapeutic development. The elucidation of Parkin's crystal structure and better understanding of possible posttranslational modifications (i.e. phosphorylation, ubiquitination, etc.) that regulate Parkin's enzymatic activity suggest that this protein is a therapeutic drug target in many human diseases. Here we review Parkin's role in health and disease and discuss the effects of self-ubiquitination and deubiquitination on Parkin activity. This review provides further evidence showing the longitudinal effects of Parkin deletion on mitochondrial function, oxidative stress and neurotransmitter balance in vivo using high-frequency (1)H/(13)C NMR spectroscopy. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 07/2015; 15(5). DOI:10.1159/000430888
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    ABSTRACT: β-Synuclein (β-Syn) is a member of the highly homologous synuclein protein family. The most prominent family member, α-synuclein (α-Syn), abnormally accumulates in so-called Lewy bodies, one of the major pathological hallmarks of α-synucleinopathies. Notably, parts of the peptide backbone, called the nonamyloid component, are also found in amyloid plaques. However, β-Syn seems to have beneficial effects by reducing α-Syn aggregation, and amyloid antiaggregatory activity has been described. The aim of the study was to analyze if wild-type β-Syn can counteract functional and pathological changes in a murine Alzheimer model over different time periods. At the onset of pathology, lentiviral particles expressing human β-Syn were injected into the hippocampus of transgenic mice overexpressing human amyloid precursor protein with Swedish and London mutations (APPSL). An empty vector served as the control. Behavioral analyses were performed 1, 3 and 6 months after injection followed by biochemical and histological examinations of brain samples. β-Syn expression was locally concentrated and rather modest, but nevertheless changed its effect on APP expression and plaque load in a time- and concentration-dependent manner. Interestingly, the phosphorylation of glycogen synthase kinase 3 beta was enhanced in APPSL mice expressing human β-Syn, but an inverse trend was observed in wild-type animals. The initially reported beneficial effects of β-Syn could be partially reproduced, but locally elevated levels of β-Syn might also cause neurodegeneration. To enlighten the controversial pathological mechanism of β-Syn, further examinations considering the relationship between concentration and exposure time of β-Syn are needed. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 06/2015; 15(4). DOI:10.1159/000430952
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    ABSTRACT: We reported a procedure of serum anticholinergic activity (SAA) measurement and the reliability and reproducibility of the receptor binding assay, and we also described the usefulness of SAA measurement reflecting the anticholinergic activity (AA) in the central nervous system (CNS). According to the results of a 10 times repeated measurement of standard atropine binding, the relative error was between -5.5 and +3.7%, and we considered that measurement of SAA in our studies is accurate and validated. Downregulation of acetylcholine activates inflammation in both CNS and peripheral tissue, which causes AA in both sites. Therefore, changes of AA in the CNS link with SAA in the peripheral system even if a substance having AA does not penetrate through the blood-brain barrier. Then we redescribe issues that require attention in the measurement of SAA. It is generally defined that any SAA greater than the detection limit of a quantitative atropine equivalent level (≥1.95 nM in our study) is positive. According to previous studies, SAA is considered to be positive when its atropine equivalent is ≥1.95 nM and undetectable when this is <1.95 nM. Nevertheless, as a low SAA can act as AA in the CNS, we should assume that SAA might also be positive if its marker concentration is between 0 and 1.95 nM. In addition, SAA should be measured around 11 a.m. or somewhat later because of the diurnal rhythm of cortisol in humans. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 06/2015; 15(3):134-9. DOI:10.1159/000381483
  • Neurodegenerative Diseases 06/2015; 15(3):131-3. DOI:10.1159/000381482
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    ABSTRACT: We report a case of a 54-year-old woman presenting with amnesia, apathy, work-related difficulties and mental stress. At presentation, her Mini-Mental State Examination score was 27 and her serum anticholinergic activity (SAA) was positive without medication or recent physical illnesses. In addition, magnetic resonance imaging revealed mild atrophy of the frontal and temporal lobes, with a relatively intact hippocampus. Consequently, we diagnosed mild cognitive impairment due to Alzheimer's disease and prescribed a cholinesterase inhibitor (donepezil, 10 mg/day); her SAA fully disappeared and clinical symptoms partially resolved. Addition of duloxetine coupled with environmental adjustments caused her cognitive function to return to a normal level, so we diagnosed pseudodementia due to depression. In this case, we believe that the simultaneous cholinergic burden and mental stress led to positive SAA, which made it reasonable to prescribe a cholinesterase inhibitor to ameliorate the associated acetylcholine hypoactivity. We believe that it is essential to recognize the importance of prescribing a cholinesterase inhibitor for specific patients, even those with pseudodementia, to control their clinical symptoms. Moreover, SAA might be a useful biomarker for identifying this subgroup of patients. We propose that anticholinergic activity appears endogenously in mood disorders (depression and bipolar disorder) and set out our rationalization for this hypothesis. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 06/2015; 15(3):175-81. DOI:10.1159/000381525
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    ABSTRACT: In this article, we review and repropose our hypothesis of the endogenous appearance of anticholinergic activity (AA) in Alzheimer's disease (AD). First, we introduce our previous articles and speculate that, because acetylcholine (ACh) regulates both cognitive function and inflammation, downregulation of this neurotransmitter causes upregulation of the inflammatory system. AA then appears endogenously with the production of cytokines and the downregulation of ACh in AD. To support our hypothesis, we present a female AD patient whose AA was considered to occur endogenously through her AD pathology. Her serum anticholinergic activity (SAA) was positive at her first visit to our memory clinic, was negative at the 1-year and 2-year follow-up visits, and had become positive again by 3 years. We speculate that the initial positive SAA was related to her AD pathology plus mental stress, and that her SAA at 3 years was related to her AD pathology only. Consequently, we believe that 2 patterns of SAA positivity (and therefore AA) exist. One occurs when the downregulation of ACh reaches a critical level, and the other occurs with the addition of some other factor such as medication, induced illness or mental stress that causes AA to affect AD pathology. Finally, we consider the pharmacotherapy of AD based on the proposed hypothesis and conclude that cholinesterase inhibitors can be used to prevent rapid disease progression, whereas N-methyl-D-aspartate receptor antagonists should be reserved for the treatment of AD that is already in a stage of rapid progression. We also propose a staging schema for patients with AD. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 06/2015; 15(3):149-56. DOI:10.1159/000381511
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    ABSTRACT: We have previously proposed a hypothesis in which we argue that anticholinergic activity (AA) appears endogenously in Alzheimer's disease (AD). Acetylcholine (ACh) controls both cognitive function and inflammation. Consequently, when the downregulation of ACh reaches critical levels, the inflammatory system is upregulated and proinflammatory cytokines with AA appear. However, factors other than downregulation of ACh can produce AA; even if ACh downregulation does not reach critical levels, AA can still appear if one of these other AA-producing factors is added. These factors can include neurocognitive disorders other than AD, such as delirium and Lewy body disease (LBD). In delirium, ACh downregulation fails to reach critical levels, but AA appears due to the use of medicines, physical illnesses or mental stress (termed 'AA inserts'). In LBD, we speculate that AA appears endogenously, even in the absence of severe cognitive dysfunction, for 2 reasons. One reason is that patterns of ACh deterioration are different in LBD from those in AD, with synergistic actions between amyloid and α-synuclein thought to cause additional or severe symptoms that accelerate the disease course. The second reason is that AA occurs through disinhibition by reduced cortisol levels that result from severe autonomic parasympathetic dysfunction in LBD. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 06/2015; 15(3):162-7. DOI:10.1159/000381522
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    ABSTRACT: We previously proposed the hypothesis of endogenous anticholinergic activity (AA) in Alzheimer's disease (AD). According to this hypothesis, the downregulation of acetylcholine seen in AD is associated with upregulation/hyperactivity of N-methyl-D-aspartate receptor (NMDAR). The hyperactivation of NMDAR then induces inflammation, which, in turn, causes AA to appear endogenously. Based on this hypothesis, we commented that cholinesterase inhibitors (ChEIs) are 'preventative' therapy for AD and NMDAR antagonists are the true 'treatment' for AD. We also noted that ChEIs, such as donepezil, could treat delirium. Moreover, we proposed measuring serum anticholinergic activity in patients, particularly AD patients, in out-of-hospital pharmacies to monitor the anticholinergic burden for targeted treatment. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 06/2015; 15(3):157-61. DOI:10.1159/000381513
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    ABSTRACT: In this article, we review the downregulation of acetylcholinergic activity in schizophrenia and discuss the similarity and difference between Alzheimer's disease (AD) and schizophrenia in terms of acetylcholine (ACh) and anticholinergic activity (AA); then, we propose the use of cognition-enhancing therapy for schizophrenia. As ACh regulates an inflammatory system, when the cholinergic system is downregulated to a critical level, the inflammatory system is activated. We consider the possibility that AA appears endogenously in AD and accelerates AD pathology. This hypothesis can also be applied to schizophrenia. In fact, even before the onset of the disorder, in the prodromal phase of schizophrenia, cognitive dysfunction exists, and antibodies against astrocyte muscarinic-1 and muscarinic-2 receptors are present in the serum of patients with the paranoid type of schizophrenia. Then we noted that the prodromal phase in schizophrenia might correspond to the mild stage in AD and the acute phase to moderate stage concerning AA. We also think that we should enhance cognition in schizophrenia even in the prodromal phase because as mentioned above, downregulation of ACh is prominent in schizophrenia even in the prodromal phase. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 06/2015; 15(3):168-74. DOI:10.1159/000381523
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    ABSTRACT: The brain of Alzheimer's disease (AD) patients is characterized by neurodegeneration, especially an acetylcholine (ACh) neuronal deficit with accumulation of β-amyloid protein, which leads to oxygen stress and inflammation. The active oxygen directly damages the neuron by increasing intracellular Ca(2+). The inflammation is due to activation of the microglia, thereby producing cytokines which inhibit the production of brain-derived neurotrophic factor (BDNF). As the BDNF acts by neuronal protection, synaptogenesis and neurogenesis, the reduction of BDNF in the brain of AD patients worsens the symptoms of AD. On the other hand, treatment of AD patients with a cholinesterase inhibitor enhances ACh activity and inhibits inflammation. Then the expression of BDNF is restored and neuroprotection reestablished. However, there are several reports which showed controversial results concerning the relationship between BDNF and AD. We speculate that BDNF is related to some neurocognitive process and reflects neuronal activity in other neurodegenerative and neuropsychiatric disorders and that in the mild cognitive impairment stage, BDNF and choline acetyltransferase (ChAT) activities are hyperactivated because of a compensatory mechanism of AD pathology. In contrast, in the mild stage of AD, BDNF and ChAT activity are downregulated. © 2015 S. Karger AG, Basel.
    Neurodegenerative Diseases 06/2015; 15(3):182-7. DOI:10.1159/000381531