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 · Apr 2012
Functional connectivity tracks clinical deterioration in Alzheimer's disease.
While resting state functional connectivity has been shown to decrease in patients with mild and/or moderate Alzheimer's disease, it is not yet known how functional connectivity changes in patients as the disease progresses. Furthermore, it has been noted that the default mode network is not as homogenous as previously assumed and several fractionations of the network have been proposed. Here, we separately investigated the modulation of 3 default mode subnetworks, as identified with group independent component analysis, by comparing Alzheimer's disease patients to healthy controls and by assessing connectivity changes over time. ⋯ At follow-up, functional connectivity decreased across all default mode systems in patients. Our results suggest that earlier in the disease, regions of the posterior default mode network start to disengage whereas regions within the anterior and ventral networks enhance their connectivity. However, as the disease progresses, connectivity within all systems eventually deteriorates.