Lowered Levels of Carbonyl Proteins after Vitamin B Supplementation in Patients with Mild Cognitive Impairment and Alzheimer's Disease
Conclusion: Vitamin supplementation leads to reduced levels of CPs in patients. Pearson's correlation coefficient shows a negative relation (r = -0.69) between CPs and MMSE. Future trials should assess whether CPs might be suitable markers for monitoring of demented patients.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - November 20, 2015 Category: Neurology Source Type: research
Defining the Genetic Architecture of Alzheimer's Disease: Where Next
Background: Late-onset Alzheimer's disease is a genetically complex disorder. For 17 years, APOE was the only known susceptibility gene for disease. Through mostly genome-wide association studies, 25 loci are now known to associate with late-onset Alzheimer's disease. These susceptibility loci are not randomly distributed with respect to their functions. In fact, pathway analysis implicates significant enrichment of immunity, endocytosis, cholesterol metabolism, and ubiquitination in disease. Summary: Twenty-five loci have now been reliably shown to associate with Alzheimer's disease. However, a significant proportion of g...
Source: Neurodegenerative Diseases - November 11, 2015 Category: Neurology Source Type: research
Cerebrospinal Fluid Biomarkers Predict Clinical Evolution in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment
Conclusion: An abnormal AD CSF biomarker profile in predementia subjects is a powerful predictor of cognitive and/or functional decline in the medium term.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - November 11, 2015 Category: Neurology Source Type: research
Discriminative Power of Arterial Spin Labeling Magnetic Resonance Imaging and 18F-Fluorodeoxyglucose Positron Emission Tomography Changes for Amyloid-β-Positive Subjects in the Alzheimer's Disease Continuum
Conclusion: The results comparing measurements of CBF to CMRgl add to previous reports that MRI-measured CBF has a similar diagnostic ability to detect AD as has FDG-PET. Our findings that CBF and CMRgl changes occur in different brain regions in Aβ+ subjects across the AD continuum compared with Aβ- CN subjects may be the result of methodological differences. Alternatively, these findings may signal alterations in neurovascular coupling which alter relationships between brain perfusion and glucose metabolism in the AD continuum.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - November 11, 2015 Category: Neurology Source Type: research
Genetic Disorders with Tau Pathology: A Review of the Literature and Report of Two Patients with Tauopathy and Positive Family Histories
Background: Tauopathies are a group of neurodegenerative disorders characterized by the pathological accumulation of hyperphosphorylated and insoluble tau protein within neurons and glia. Although most cases are sporadic, hereditary tauopathies have also been reported. Summary: In this article, we review genetic disorders in which tau pathology has been reported and present two novel families with primary tauopathies. Mutations in the microtubule-associated protein tau gene (MAPT) cause a small subset of primary tauopathies. Mutations in 21 other genes and an 18q deletion syndrome have also been reported to be associated w...
Source: Neurodegenerative Diseases - November 10, 2015 Category: Neurology Source Type: research
Tau Immunotherapy
In recent years, tau immunotherapy has advanced from proof-of-concept studies [Sigurdsson EM, NIH R01AG020197, 2001; Asuni AA, et al: J Neurosci 2007;27:9115-9129], which have now been confirmed and extended by us and others. Phase I clinical trials on active and passive tau immunizations are being conducted, with several additional passive tau antibody trials likely to be initiated in the near future for Alzheimer's disease and other tauopathies. Because tau pathology correlates better with the degree of dementia than amyloid-β (Aβ) pathology, greater clinical efficacy may be achieved by clearing tau than Aβ aggregates...
Source: Neurodegenerative Diseases - November 10, 2015 Category: Neurology Source Type: research
Higher Frequency and Complexity of Sleep Disturbances in Dementia with Lewy Bodies as Compared to Alzheimer's Disease
Conclusions: Sleep problems are more common in DLB patients compared to AD, and are associated with more clinical impairment. DLB patients frequently have several sleep problems occurring simultaneously, which suggests a need for screening and accurate assessment of sleep in DLB.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - November 10, 2015 Category: Neurology Source Type: research
Impaired Eukaryotic Elongation Factor 1A Expression in Alzheimer's Disease
Conclusion: Dysregulation of eEF1A and its associated signaling pathways might represent novel molecular mechanisms underlying AD pathogenesis. Further investigation is necessary to determine whether eEF1A is a viable therapeutic target for AD and other cognitive syndromes.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - November 10, 2015 Category: Neurology Source Type: research
Tau as the Converging Protein between Chronic Stress and Alzheimer's Disease Synaptic Pathology
Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with a complex physiopathology and still undefined initiators. Several risk factors have been suggested for AD with recent evidence supporting an etiopathogenic role of chronic environmental stress and glucocorticoids (GCs, stress hormones) in the development of the disease. Indeed, both AD and chronic stress are associated with neuronal atrophy, synaptic loss and cognitive impairment. Our previous studies have demonstrated the aggravating role of stress and GCs on AD pathology, including Tau hyperphosphorylation and aggregation and cogniti...
Source: Neurodegenerative Diseases - November 10, 2015 Category: Neurology Source Type: research
Defining the Genetic Architecture of Alzheimer's Disease: Where Next?
Background: Late-onset Alzheimer's disease is a genetically complex disorder. For 17 years, APOE was the only known susceptibility gene for disease. Through mostly genome-wide association studies, 25 loci are now known to associate with late-onset Alzheimer's disease. These susceptibility loci are not randomly distributed with respect to their functions. In fact, pathway analysis implicates significant enrichment of immunity, endocytosis, cholesterol metabolism, and ubiquitination in disease. Summary: Twenty-five loci have now been reliably shown to associate with Alzheimer's disease. However, a significant proportion of g...
Source: Neurodegenerative Diseases - November 10, 2015 Category: Neurology Source Type: research
Clinicopathological Correlations and Concomitant Pathologies in Rapidly Progressive Dementia: A Brain Bank Series
Conclusions: Prion diseases were accurately identified in our series. In contrast, non-prion RPD diagnosis was poor while the patients were still alive, supporting the need for better diagnostic tools and confirmatory neuropathological studies. The presence of concomitant AD pathology in RPD should be taken into account in the interpretation of amyloid biomarkers.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - November 2, 2015 Category: Neurology Source Type: research
Evaluating Behavior in Mouse Models of the Behavioral Variant of Frontotemporal Dementia: Which Test for Which Symptom?
The behavioral variant of frontotemporal dementia (bvFTD) is a neurodegenerative disease affecting people in their early sixties, characterized by dramatic changes in individual and social behavior. Despite the heterogeneity in the presentation of the clinical symptoms of bvFTD, some characteristic changes can be highlighted. Social disinhibition, changes in food preferences as well as loss of empathy and apathy are commonly described. This is accompanied by a characteristic and dramatic atrophy of the prefrontal cortex with the accumulation of protein aggregates in the neurons in this area. Several causative mutations in ...
Source: Neurodegenerative Diseases - October 31, 2015 Category: Neurology Source Type: research
The Effect of Aβ1-42 Oligomers on APP Processing and Aβ1-40 Generation in Cultured U-373 Astrocytes
Conclusions: These results suggest that activated astrocytes can contribute to the development of AD by enhancing levels and processing of APP leading to an increased production/secretion of Aβ-related peptides.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - October 20, 2015 Category: Neurology Source Type: research
Parkinson's Disease Case Ascertainment in the EPIC Cohort: The NeuroEPIC4PD Study
Conclusions: This exercise proved that it is feasible to ascertain PD in large population-based cohort studies and offers a potential framework to be replicated in similar studies.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - September 17, 2015 Category: Neurology Source Type: research
Uncoupling of Protein Aggregation and Neurodegeneration in a Mouse Amyotrophic Lateral Sclerosis Model
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 ...
Source: Neurodegenerative Diseases - September 12, 2015 Category: Neurology Source Type: research
