A NOVEL PRESENILIN-1 MUTATION RESULTING IN FAMILIAL ALZHEIMERS-DISEASE WITH AN ONSET AGE OF 29 YEARS

WE have identified a novel Alzheimer's disease family in which affecte d subjects had a very young age of onset (range 29-35 years). Neuropat hological confirmation of the diagnosis was obtained for one patient. Molecular analysis shows that within this family the disease results f rom a missense mutation at codon 235 of the presenilin 1 (PS-1) gene. Two patients had exhibited generalized tonico-clonic seizures several years before the onset of dementia. Whether this particular clinical f eature is a consequence of the PS-I mutation remains to be established . The Leu235Pro mutation is, to our knowledge, the PS-I mutation assoc iated with the youngest age of AD onset, which suggests that it has a drastic effect on PS-1 function.