A NOVEL POLISH PRESENILIN-1 MUTATION (P117L) IS ASSOCIATED WITH FAMILIAL ALZHEIMERS-DISEASE AND LEADS TO DEATH AS EARLY AS THE AGE OF 28 YEARS

THE majority of early-onset familial Alzheimer's disease (FAD) is asso ciated with mutations in the presenilin-1 (PS1) gene. We describe a no vel Polish PS1 mutation of Pro117Leu, associated with the earliest ave rage age of onset and death so far reported in a PS-linked, FAD kindre d. Human kidney 293 and mouse neuroblastoma N2a cells were stably tran sfected with wild-type and PS1 P117L. There was a significant increase in the amyloid beta 42/40 ratio in the N2a P117L PS1 transfected cell s compared with N2a transfected with wild-type PS1. What role PS has i n the pathogenesis of AD remains to be determined, however, the severi ty of the clinical picture associated with this PS1 mutation stresses the importance of presenilin.