AMYLOID beta-peptide (A beta) is a major component of neuritic plaques
, a feature of Alzheimer's disease (AD) brains. Recently, we showed th
at A beta adopts two major conformational states in solution, which di
ffer in their abilities to form amyloid. These are a highly amyloidoge
nic conformer (A beta ac) with a high content of beta-sheet and a slow
ly amyloidogenic conformer (A beta nac) with a random coil conformatio
n. Apolipoprotein E (apoE), particularly the E4 isoform, which is gene
tically associated with AD, binds to A beta and modulates fibrillogene
sis in vitro. In the present work, the influence of apoE on the confor
mation 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 t
hat 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