Plaque Research Today is a free monthly online journal that collates and summarizes the latest research about Plaque, including details on dentistry, brushing, oral hygiene, mouthwash.

Surface structure of amyloid-beta fibrils contributes to cytotoxicity.

Yoshiike Y, Akagi T, Takashima A

Laboratory for Alzheimer's Disease, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan.

Amyloid beta (Abeta) toxicity has been hypothesized to initiate the pathogenesis of Alzheimer's disease (AD). The characteristic fibrillar morphology of Abeta-aggregates, that constitute the main components of senile plaque, has long been considered to account for the neurotoxicity. But recent reports argue against a primary role for mature fibrils in AD pathogenesis because of the lack of a robust correlation between the severity of neurological impairment and the extent of amyloid deposition. Toxicity from the soluble prefibrillar intermediate entity of aggregates often called oligomer has recently proposed a plausible explanation for this inconsistency. An alternative explanation is based on the observation that certain amyloid fibril morphologies are more toxic than others, indicating that not all amyloid fibrils are equally toxic. Here, we report that it is not only the beta-sheeted fibrillar structure but also the surface physicochemical composition that affects the toxicity of Abeta fibrils. For the first time, colloidal gold was used to visualize by electron microscopy positive-charge clusters on Abeta fibrils. Chemical modifications as well as point-mutated Abeta synthesis techniques were applied to change the surface structures of Abeta and to show how local structure affects surface properties that are responsible for electrostatic and hydrophobic interactions with cells. We also report that covering the surface of Abeta fibers with myelin basic protein, which has surface properties contrary to those of Abeta, suppresses Abeta toxicity. On the basis of these results, we propose that the surface structure of Abeta fibrils plays an important role in Abeta toxicity.

Published 21 August 2007 in Biochemistry, 46(34): 9805-12.
Full-text of this article is available online (may require subscription).

© 2004-2008 Plaque Research Today. All Rights Reserved.