早期発症型家族性アルツハイマー病の原因遺伝子S182 (Presenilin-1) の mutation analysis と biological function について

抄録

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 colon 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 distingguishes Alzheimer's disease associated with PS I mutations from other early-onset familial Alzheimer's disease. This implas that the variable phenotypes of familial Alzheimer's, disease might be aftribatable to factors other than the PS gene.