Mutations in the presenilln 1 (PS1) gene on chromosome 14 are a major cause of autosomal dominant, early-onset Alzheimer's disease. Here, we show that transfecting cells with several mutant, but not wild-type, PS1 cDNAs alters the processing of the amyloid precursor protein (APP) such that more Aβ42(43) is produced, confirming and extending several recent reports. The most effective mutation in this regard was the exon 9 splice-out mutation (Δ9). The correlation between the size of the effect on APP processing and the age of onset of disease assessed in families with the mutations was not informative, and the possible reasons for this are discussed.
ASJC Scopus subject areas
- Clinical Neurology