Screening of the mis-sense mutation producing the 717Val-->Ile substitution in the amyloid precursor protein in Japanese familial and sporadic Alzheimer's disease.

We investigated a C to T transition at base pair 2149 in the amyloid precursor protein gene in 41 Japanese cases of early-onset familial Alzheimer's disease (FAD), late-onset FAD and sporadic Alzheimer's disease (AD) by polymerase chain reaction and restriction enzyme polymorphism with BclI. Among 9 early-onset FAD patients derived from independent families, only one patient had the mis-sense mutation. Neither 5 patients with late-onset FAD nor 27 patients with sporadic AD had the mutation. Our result and the previous reports from Japan indicate that this type of mis-sense mutation is present in several cases of Japanese early-onset FAD. On the other hand, our data suggest that this mutation is not a common cause of Japanese early-onset FAD. Moreover, this mutation could be absent in late-onset FAD and sporadic AD in Japan. Because the mutation has been reported to be rare in Caucasian early-onset FAD and to be absent in Caucasian late-onset FAD and sporadic AD, the situation of this mutation in Alzheimer's disease may be common beyond the ethnic background.