Presenilin 1 binds to amyloid precursor protein directly.

Mutations in the presenilin genes are associated with early onset familial Alzheimer's disease and lead to accumulation of beta-amyloid peptide in the brain of patients, suggesting that presenilin abnormalities induce pathological processing of amyloid precursor protein (APP) in Alzheimer's disease. For the understanding of pathogenesis in this type of familal Alzheimer disease, it is important to know whether presenilins are directly involved in the metabolism of beta-amyloid or not. To test whether presenilin 1 (PS1) directly binds to APP, we performed two-hybrid interaction assays between these proteins in yeast cells by using bait plasmids for normal and mutant PS1 and prey plasmids for APP fragments corresponding to the different molecular portions. Positive interaction was observed in any combination between PS1 bait plasmids and APP prey plasmids. Therefore, our results show that PS1 binds to APP directly and suggest that the PS1 protein itself is involved in the metabolism of beta-amyloid peptide.