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- W2000499212 abstract "Alzheimer's disease (AD) is a dementia that affects elderly individuals in escalating numbers due to an unprecedented increase in life expectancy. At present, there are more than 5 million Americans with AD. One of the most relevant neuropathological lesions in the AD brain is the abundant accumulation of aggregated Aβ peptides in senile and diffuse plaques in the cortex, in the walls of cerebral vessels and in soluble oligomeric forms as well as in membrane raft microdomains. Encouraged by the recent suggestion that membrane bound Aβ peptides may play a pivotal role in the pathophysiology of AD, beyond the accepted tenet of pathological extracellular fibrillar and soluble Aβ, we investigated the membrane associated peptides as another important locus for Aβ peptide accumulation. The Aβ peptides in plasma membrane and raft microdomain preparations present in the gray matter of AD and non-demented (ND) controls were purified by differential centrifugation, tresyl-dextran-lectin-affinity fractionation and sucrose gradients. The Aβ peptides in the enriched plasma membrane fractions were dissociated from the lipid bi-layer and solubilized by concentrated formic acid. The delipidated Aβ peptides were purified by size exclusion and reverse-phase chromatography and characterized utilizing Western blots and mass spectrometry. Aβ40 and Aβ42 monomeric and oligomeric forms are associated to cortical plasma membranes and raft microdomains of the cerebral cortex of AD and ND control individuals. Plasma membrane bound Aβ demonstrated important physicochemical alterations between AD and ND control individuals. These differences may in part explain the neuropathological features and clinical manifestations observed in AD." @default.
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- W2000499212 date "2008-07-01" @default.
- W2000499212 modified "2023-09-27" @default.
- W2000499212 title "P1-474: Membrane bound Aβ peptides in Alzheimer's disease and nondemented subjects" @default.
- W2000499212 doi "https://doi.org/10.1016/j.jalz.2008.05.1057" @default.
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