PRESENILIN-I BINDS TO AMYLOID PRECURSOR PROTEIN DIRECTLY

Mutations in the presenilin genres are associated with early onset fam ilial Alzheimer's disease and lead to accumulation of beta-amyloid pep tide in the brain of patients, suggesting that presenilin abnormalitie s induce pathological processing of amyloid precursor protein (APP) in Alzheimer's disease. Far the understanding of pathogenesis in this ty pe of familiar Alzheimer disease, it is important to know whether pres enilins are directly involved in the metabolism of beta-amyloid or not , To test whether presenilin 1 (PS1) directly binds to APP, we perform ed two-hybrid interaction assays between these proteins in yeast cells by using bait plasmids for normal and mutant PS1 and prey plasmids fo r APP fragments corresponding to the different molecular portions, Pos itive interaction was observed in any combination between PS1 bait pla smids and APP prey plasmids, Therefore, our results show that PS1 bind s to APP directly and suggest that tame PS1 protein itself is involved in the metabolism of beta-amyloid peptide. (C) 1997 Academic Press.