ACETYLCHOLINESTERASE, A SENILE PLAQUE COMPONENT, AFFECTS THE FIBRILLOGENESIS OF AMYLOID-BETA-PEPTIDES

Acetylcholinesterase (AChE) colocalizes with amyloid-beta peptide (A b eta) deposits present in the brain of Alzheimer's patients. Recent stu dies showed that A beta(1-40) Can adopt two different conformational s tates in solution (an amyloidogenic conformer, A beta ac, and a non-am yloidogenic conformer, A beta nac) which have distinct abilities to fo rm amyloid fibrils. We report here that AChE binds A beta nac and acce lerates amyloid formation by the same peptide. No such effect was obse rved with A beta ac, the amyloidogenic conformer, suggesting that AChE acts as a 'pathological chaperone' inducing a conformational transiti on from A beta nac into A beta ac in vitro.