title: [Mutation analysis of S182 (presenilin-I) in patients with familial Alzheimer's disease and its biological function].
abstract: We report the clinical and neuropathologic phenotypes associated with two missence mutations in the presenilin I (PS I) gene in Japanese patients with early-onset familial Alzheimer's disease. The AM/JPN1 family showed a missense mutation (C-->T) which is predicted to cause an Alanine to Valine missense substitution at codon 260 (A260V). The disease in the members of this family had a mean age-of-onset of 40.3 years old (the range of disease is 8-19 years). Neuropathologic studies of two members of AM/JPN1 pedigree showed wide-spread senile plaques, neurofibrillary tangles, and neuronal loss, as well abundant perivascular subpial amyloid deposits in the Virchow-Robin spaces and Pick-like intraneuronal inclusions in the dentate gyrus. In the second pedigree transmitting a C-->T nucleotide substitution leading to the missense mutation of Alanine to Valine at codon 285 (A285V), the disease had a later age of onset (mean, 51 years) but a more rapid course. Comparison of the disease phenotypes associated with other missense mutations in exon 9 of PSI reveals no obvious clinical or pathological phenotype that uniquely distinguishes Alzheimer's disease associated with PS I mutations from other early-onset familial Alzheimer's disease. This implies that the variable phenotypes of familial Alzheimer's, disease might be attributable to factors other than the PS gene.
authors.affiliation: Department of Neurology, Gunnma University School of Medicine.
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D053764:Presenilin-1
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1