INCREASED A-BETA 42(43)-PLAQUE DEPOSITION IN EARLY-ONSET FAMILIAL ALZHEIMERS-DISEASE BRAINS WITH THE DELETION OF EXON-9 AND THE MISSENSE POINT MUTATION (H163R) IN THE PS-1 GENE

Cerebral amyloid deposition is a neuropathological hallmark for Alzhei mer's disease (AD). Immunohistochemical analysis of two A beta species (A beta 42/43 and A beta 40) deposition was undertaken using the carb oxyl end-specific antibodies to determine the molecular alteration of these species in the brains of patients whose presenilin 1 (PS-1) gene , the major causative gene for the early-onset familial AD, bears the point mutation (H163R) and the deletion of exon 9. We found a marked i ncrease in A beta 42-plaque deposition in brains of patients with PS-1 mutations compared with that in brains of those with sporadic AD. The results of immunohistochemical analysis indicate that both mutation a nd deletion in the PS-1 gene promote deposition of A beta 42-plaques i ndicating the pathological association of PS-1 and beta APP/A beta 42 in early-onset familial AD. (C) 1997 Elsevier Science Ireland Ltd.