PCR-SSCP SCREENING OF β-AMYLOID PRECURSOR PROTEIN MUTATIONS IN TWO JAPANESE PEDIGREES WITH FAMILIAL EARLY ONSET ALZHEIMER’S DISEASE

Five different types of point mutation of the β-amyloid precursor gene (APP) have been reported to cosegregate with familial Alzheimer’s disease (FAD) in each of examined pedigrees (Table 1). Here we report a screening result of the APP gene mutations in two Japanese pedigrees with FAD of an early onset type which have previously been reported (2, 3). Primer pairs corresponding respectively to each of 19 exons of the APP gene were designed. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis was performed on genomic DNA of one affected member from each of these two pedigrees. In addition, a pair of primers was designed to assess specifically codon 717 of the APP gene even in the poorly-preserved sample of genomic DNA. PCR-SSCP analysis of all 19 exons of the APP gene of both patients did not show any mutations, but disclosed one polymorphism in the intron 9. Sequencing of exons 16 and 17 of the APP gene in both patients, where all reported pathogenic mutations are located, revealed normal sequences. The results support that the genetic defect causing FAD is heterogeneous and that most cases with FAD are apparently due to the gene-defect of other than the APP gene.