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

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 a 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