Sequence analysis of presenilin-1 gene mutation in Japanese Alzheimer's disease patients.

The mutations of presenilins (PSs) gene and their clinicopathological correlations to Alzheimer's disease (AD) have lately attracted considerable attention. In this report we analyzed fifteen Japanese familial Alzheimer's disease (FAD) including 12 early-onset FAD and 13 sporadic AD patients for the mutation of PS-1 gene by direct sequence analysis. We found the mutations, G384A, E280A in two FAD and H163R in one sporadic AD patient, and no N1411 or M239V mutation in PS-2 gene, and no mutation in exons 16 and 17 in amyloid precursor protein (APP) gene. Families in which we failed to find the mutation by this screening may have mutations elsewhere in PSs or in APP gene, or yet unidentified other AD loci may exist. This is the first report to find a sporadic AD patient having PS-1 mutation.