Neurobiology of aging
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Neurobiology of aging · Apr 2012
VCP mutations in familial and sporadic amyotrophic lateral sclerosis.
Mutations in the valosin-containing protein (VCP) gene were recently reported to be the cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases. VCP mutations are known to cause inclusion body myopathy (IBM) with Paget's disease (PDB) and frontotemporal dementia (FTD). The presence of VCP mutations in patients with sporadic ALS, sporadic ALS-FTD, and progressive muscular atrophy (PMA), a known clinical mimic of inclusion body myopathy, is not known. ⋯ I114V mutation to be a rare benign polymorphism. VCP mutations are a rare cause of familial ALS. The role of VCP mutations in sporadic ALS, if present, appears limited.
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Neurobiology of aging · Apr 2012
Regulation of β-amyloid level in the brain of rats with cerebrovascular hypoperfusion.
Cerebrovascular hypoperfusion occurs prior to clinical symptoms of Alzheimer's disease (AD) and represents the most accurate indicator predicting whether an individual develops AD in a future time. In order to explore the contribution of cerebrovascular hypoperfusion to AD, cerebrovascular hypoperfusion induced by bilateral carotid occlusion surgery in adult rats was used to investigate its impacts on spatial memory, amyloid-β protein (Aβ) production and clearance in the brain. The progressive spatial memory deficits were observed through Morris water maze test of the rats with cerebrovascular hypoperfusion induced by occlusion surgery. ⋯ Western blot and immunohistochemisty studies further revealed that cerebrovascular hypoperfusion could induce abnormal expression of β-amyloid receptor proteins including the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein-1 (LRP-1), and result in a shift of immunoreactivity between neurons and vasculatures. Taken together, our results suggested that chronic cerebrovascular hypoperfusion could cause memory impairment and Aβ accumulation in brain associated with increased generation and impaired clearance of Aβ. Cerebrovascular hypoperfusion plays an important role in the pathogenesis and development of AD.
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Neurobiology of aging · Feb 2012
APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory.
Both leukocyte telomere length and the apolipoprotein ε4 allele have been associated with mortality, cardiovascular disease, cognition, and dementia. The authors investigated whether leukocyte telomere length was associated with APOE genotype or cognitive abilities in the context of APOE genotype. The setting for this cross-sectional study was 427 nondemented individuals aged 41-81 yr. ⋯ In conclusion, APOE ε4 carriers had longer telomeres compared with non-carriers, but higher rate of attrition. Among them, longer telomeres predicted worse performance on episodic memory tasks. These observations suggest that the ε4 allele is associated with abnormal cell turnover of functional and possibly clinical significance.
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Neurobiology of aging · Feb 2012
Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice.
Diabetes is a risk factor for Alzheimer's disease. We tested the effects of Val(8)GLP-1, an enzyme-resistant analogue of the incretin hormone glucagon-like peptide 1 originally developed to treat diabetes in a mouse model of Alzheimer's disease that expresses mutated amyloid precursor protein (APP) and presenilin-1. We tested long term potentiation (LTP) of synaptic plasticity, inflammation response, and plaque formation. ⋯ The number of beta-amyloid plaques and microglia activation in the cortex increased with age but was not reduced by Val(8)GLP-1. In 18-month-old mice, however, the number of Congo red positive dense-core amyloid plaques was reduced. Treatment with Val(8)GLP-1 might prevent or delay neurodegenerative processes.
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Neurobiology of aging · Jan 2012
Multiple DTI index analysis in normal aging, amnestic MCI and AD. Relationship with neuropsychological performance.
White matter (WM) damage has been reported in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) in diffusion tensor imaging (DTI) studies. It is, however, unknown how the investigation of multiple tensor indexes in the same patients, can differentiate them from normal aging or relate to patients cognition. Forty-six individuals (15 healthy, 16 a-MCI and 15 AD) were included. ⋯ Present findings suggest that most DTI-derived changes in AD and a-MCI are largely secondary to gray matter atrophy. Notably however, specific DR signal increases in posterior parts of the inferior fronto-occipital and longitudinal fasciculi may reflect early WM compromise in preclinical dementia, which is independent of atrophy. Finally, global measures of integrity, particularly orientation coherence (FA) of diffusion, appear to be more closely related to the cognitive profile of our patients than indexes reflecting water movement parallel (DA) and perpendicular (DR) to the primary diffusion direction.