title: A mutation screening by DHPLC of PSEN1 and APP genes reveals no significant variation associated with the sporadic late-onset form of Alzheimer's disease.
abstract: Alzheimer's disease (AD), the most common cause of dementia in the elderly, is usually divided into familial and sporadic forms, according to family history. The familial form has often been reportedly caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes, whereas the genetic component for the sporadic form is less clear. We carried out mutation screening in exons 16 and 17 of APP, and in exons 3, 4, 5, 6, 7, 10 of PSEN1 genes in patients with the sporadic late-onset form of AD (LOAD). The aim of this study was to ascertain whether any variation in these genes, besides that of the well-known apolipoprotein E common polymorphism, could be involved in the onset of the disease. To search for the single nucleotide substitutions, we examined 172 LOAD patients by the denaturing high-performance liquid chromatography (DHPLC) technique. Only one same-sense mutation in exon 4 of PSEN1 gene (N32) was observed in this patient group. We concluded that the variation in the screened exons of the APP and PSEN1 genes, reportedly associated with familial AD, is not present in LOAD.
authors.affiliation: CNR Institute of Molecular Biology and Pathology, c/o Department of Genetics and Molecular Biology, University La Sapienza, P.le Aldo Moro 5, 00185 Rome, Italy. Renato.Scacchi@uniromal.it
authors.forename: Renato
authors.initials: R
authors.lastname: Scacchi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gambina
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Moretto
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Corbo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1