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Human serum albumin can regulate Amyloid-beta peptide fiber growth in the brain interstitium. Implications for Alzheimer's Disease.


J Biol Chem. 2012 Jun 20;


Authors: Stanyon HF, Viles JH


Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta peptide (Aβ) in the brain interstitium. Human serum albumin (HSA) binds 95 % of Aβ in blood plasma and is thought to inhibit plaque formation in peripheral tissue. However, albumin's role in binding Aβ in the cerebrospinal fluid (CSF) has been largely overlooked. Here we investigate the effect of HSA on both Aβ(1-40) and Aβ(1-42) fibril growth. We show that at micromolar CSF levels, HSA inhibits the kinetics of Aβ fibrillization, significantly increasing the lag-time and decreasing the total amount of fibrils produced. Furthermore we show that the amount of amyloid fibers generated directly correlates to the proportion of Aβ not competitively bound to albumin. Our observations suggest a significant role for HSA regulating Aβ fibril growth in the brain interstitium.

PMID: 22718756 [PubMed - as supplied by publisher]