Alzheimer's beta-amyloid peptide is conformationally modified by apolipoprotein E in vitro.

Abstract:

:Amyloid beta-peptide (A beta) is a major component of neuritic plaques, a feature of Alzheimer's disease (AD) brains. Recently, we showed that A beta adopts two major conformational states in solution, which differ in their abilities to form amyloid. These are highly amyloidogenic conformer (A beta ac) with a high content of beta-sheet and a slowly amyloidogenic conformer (A beta nac) with a random coil conformation. Apolipoprotein E (apoE), particularly the E4 isoform, which is genetically associated with AD, binds to A beta and modulates fibrillogenesis in vitro. In the present work, the influence of apoE on the conformation of A beta peptides was studied. The results suggest that, under the conditions used, apoE enhances amyloid formation by inducing the conformational transition from A beta nac into A beta ac. We propose that an important step in A beta fibrillogenesis is the transformation induced by apoE of the soluble non-amyloidogenic into the pathological amyloidogenic conformer of A beta.

journal_name

Neuroreport

journal_title

Neuroreport

authors

Soto C,Golabek A,Wisniewski T,Castaño EM

doi

10.1097/00001756-199602290-00010

subject

Has Abstract

pub_date

1996-02-29 00:00:00

pages

721-5

issue

3

eissn

0959-4965

issn

1473-558X

journal_volume

7

pub_type

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