Numerous Caucasian familial
Alzheimer's disease (
FAD) pedigrees have been described in the literature, while only 21 Japanese
FAD families have been reported to date. Here we report the clinical findings and the result of molecular genetic analysis of 4 patients from two
FAD kindreds, OS-2 and OS-3. The proband in OS-2 family has developed loss of recent memory and place disorientation age at 43. A brain CT showed severe diffuse cortical
atrophy. Her younger brother had
dementia at 42 years and her mother and other 3 siblings had also
dementia symptoms suspected to be
Alzheimer's disease. The proband in OS-3 family showed declining recent memory at 49 years and developed
dysphagia, gait disturbance and emotional incontinent with cerebral
atrophy at 52 years. His father and elder brother demonstrated
dementia signs at 60 and 54 years old, respectively. Recently it was reported that affected members from 2 Caucasian kindreds with
FAD had missense mutation in exon 17 of the gene for
amyloid precursor
protein (APP). Patients from three different Japanese kindreds with
FAD also showed the same mutation on the APP gene. Amino acid substitution (Val-Ile) at
codon 717 by this mutation is responsible for
FAD in at least some kindreds. We used genomic
DNA from 4 affected members of 2 families to determine whether the disease in these families is associated with a
APP717 mutation and the mutated
codons, 102, 117, 129, 178 and 200, on the gene for
protease-resistance
prion protein (PrP) which cause
transmissible dementia, Creutzfelt-Jacob disease (CJD) and Gerstmann-Strausler syndrome (GSS).(ABSTRACT TRUNCATED AT 250 WORDS)