GERMLINE MUTATIONAL ANALYSIS OF PRESENILIN-1 AND APP GENES IN JEWISH-ISRAELI INDIVIDUALS WITH FAMILIAL OR EARLY-ONSET ALZHEIMER-DISEASE USING DENATURING GRADIENT GEL-ELECTROPHORESIS (DGGE)

Germ line mutations in three genes have been detected in patients with familial Alzheimer's disease (FAD) and sporadic, early onset disease: amyloid precursor protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2), The relative proportions in which mutations in these genes o ccur among AD patients in Israel has not been evaluated. To that end, we screened 52 Jewish-Israeli patients with AD: 22 with sporadic, earl y-onset disease (below 65 years), and 30 with FAD. Mutation screen emp loyed denaturing gradient gel electrophoresis (DGGE) of exon-specific PCRs and restriction enzyme digest, Five patients from three different families displayed mutations within the PS-I gene: three patients of one family showed a mis-sense mutation in codon 120 (Glu 120Lys), and two other unrelated patients showed an identical mis-sense mutation in codon 318 (Glu318Gly), No patient showed an abnormal migration on DGG E (for APP) or mutant restriction digest pattern (for PS-2) genes. The se data may indicate the existence of another familial Alzheimer disea se (FAD) gene locus in the Israeli Jewish population.