FAMILIAL ALZHEIMERS-DISEASE GENES IN JAPANESE

More than 40 missense mutations and a splice-site mutation in the pres enilin 1 (PS-1) gene, two missense mutations of presenilin 2 (PS-2), a nd more than three missense mutations of amyloid precursor protein (AP P) cosegregate with early onset familial Alzheimer's disease (FAD). Tn order to determine the incidence of mutations of these genes in Japan ese patients, we screened 25 early onset FAD families, one late-onset FAD case, 33 early onset AD cases and five late-onset AD cases for mut ations in the coding regions of the genes using SSCP analysis. Four di fferent missense mutations of the PS-1 gene, including a novel mutatio n, Glu273Ala, were identified in five early onset FAD families and one missense mutation of PS-1 in one isolated AD patient. While no missen se mutations of PS-2 were detected, four silent nucleotide substitutio ns were observed. Our data indicate that PS-I mutations account for 20 .08 of early onset FAD cases in Japan. Since mutations in PS-2 and APP genes were not found in the remaining cases, which could be explained only partially by apolipoprotein E epsilon 4, important FAD genes or risk-factor genes remain to be identified. (C) 1998 Elsevier Science B .V. All rights reserved.