School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, United Kingdom.
J Biol Chem. 2012 Aug 10;287(33):28163-8. doi: 10.1074/jbc.C112.360800. Epub 2012 Jun 20.
Alzheimer disease is a neurodegenerative disorder characterized by extracellular accumulation of amyloid-β 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, the role of albumin in binding Aβ in the cerebrospinal fluid 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 cerebrospinal fluid 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.
阿尔茨海默病是一种神经退行性疾病，其特征是脑间质中淀粉样β肽（Aβ）的细胞外积累。人血清白蛋白（HSA）结合了 95%的血浆中的 Aβ，被认为可以抑制外周组织中的斑块形成。然而，白蛋白在结合脑脊液中的 Aβ方面的作用在很大程度上被忽视了。在这里，我们研究了 HSA 对 Aβ（1-40）和 Aβ（1-42）原纤维生长的影响。我们表明，在微摩尔脑脊液水平下，HSA 抑制了 Aβ原纤维形成的动力学，显著增加了滞后时间，并减少了产生的原纤维总量。此外，我们表明，生成的淀粉样纤维数量与未与白蛋白竞争结合的 Aβ比例直接相关。我们的观察结果表明 HSA 在调节脑间质中 Aβ原纤维生长方面具有重要作用。
