COMPLETE ANALYSIS OF THE PRESENILIN-1 GENE IN EARLY-ONSET ALZHEIMERS-DISEASE

THE presenilin 1 gene has recently been identified as the locus on chr omosome 14 which is responsible for a large proportion of early onset, autosomal dominantly inherited Alzheimer's disease (AD). We have eluc idated the intron/exon structure of the gene and designed intronic pri mers to enable direct sequencing of the entire coding region (10 exons ) of the presenilin gene in a large number of families. This strategy has enabled us to find a further two novel mutations in the gene. We d iscuss the distribution of mutations and the proportions of autosomal dominant AD with a mean age of onset below 60 years caused by mutation s in this gene.