1996 Fiscal Year Final Research Report Summary
Cloning the responsible gene for early-onset familial Alzheimer's disease
| Project/Area Number |
07457156
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Osaka University |
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Principal Investigator |
MIKI Tetsuro Osaka University Medical School Associate Professor, 医学部, 助教授 (00174003)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Familial Alzheimer's disease / Genetic analysis / Preseniline-1 / Positional cloning / Alzheimer's disease |
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| Research Abstract |
The pathogenesis of Alzheimer's disease (AD) remains unclear. We ascertained 56 Japanese families with early onset familial Alzheimer's disease (EOFAD ; mean onset age <65 years). Screening the known b/A4 amyloid precursor protein (APP) mutations in 13 familial AD and 69 sporadic AD by a simplified detection system of PCR product disclosed only one EOFAD with the APP 717Val-Ile mutation (AD1 locus). Four out of 6 families showing a positive linkage to AD3 locus had four different mutaitions on the presenilin 1 gene. These mutations were Val96Phe, Ile223Thr, His163Arg and splicing mutation with an AG-AA substitution at the acceptor site of intron 9. The allele frequency of APOE-e4 of late-onset and early-onset AD was significantly higher than that of agematched controls (p<0.0001). These resuts suggest that APOE-e4 (AD2 locus) is a susceptibility gene for AD in the Japanese population, regardless of the age of onset. It is probable that the risk for AD in most subjects is likely to arise from the cumulative effects of environmental factors and various genetic factors. Advance in molecular biology and molecular genetics have enabled us to easily understand the genetic factors.
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