2004 Fiscal Year Final Research Report Summary
Research of the alterations on gene regulation for pathogenesis of dementia
| Project/Area Number |
14370290
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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 |
Psychiatric science
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| Research Institution | Kobe University Graduate School of Medicine |
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Principal Investigator |
MAEDA Kiyoshi Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80116251)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAMATA Toshio Kobe University, School of Medicine, Professor, 医学部, 教授 (70214690)
YASUDA Minoru Kobe University, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (50359866)
YAMAMOTO Yasuji Kobe University, Graduate School of Medicine, Assistant, 大学院・医学系研究科, 助手 (00324921)
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| Project Period (FY) |
2002 – 2004
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| Keywords | dementia / Alzheimer's disease / cooperation of clinical research between hospitals / genetic research / satellite hospital / プレセニリン |
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| Research Abstract |
Familial Alzheimer's disease is a heterogeneous condition that has been associated with mutations in three different genes, the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes. Most familial Alzheimer patients are due to mutations in the PS1 gene, whereas mutations in the APP gene are rare. The apolipoprotein E (APOE)ε 4 allele is a major genetic risk factor for late-onset and sporadic early-onset Alzheimer's disease, and about half of Alzheimer's disease patients have at least one APOEε4 allele. An association was reported between a polymorphism in the 5'-upstream promoter region of the PSEN2 gene and late-onset, sporadic Alzheimer's disease among subjects lacking the APOEε 4 allele and younger than 65 years of a Russian population. Mutation analysis of the APP, PSEN1, and PSEN2 genes was performed. We examined 230 patients with Alzheimer's disease, along with an equal number of age-and sex-matched controls from the same community, in a Japanese population by using a chi-square test for homogeneity and a logistic regression analysis. The PSEN2 polymorphism frequencies were similar in early-onset Alzheimer's disease patients and younger controls, and in late-onset Alzheimer's disease and elderly controls. We found no evidence for a possible association between the PSEN2 polymorphism and the apolipoprotein Eε 4 allele. Our results fail to support an association of PSEN2 gene polymorphism with Alzheimer's disease. The discrepancy between our results and the results of the Russian study appear to be due to racial differences. We also found two missense mutations as well as 10 polymorphisms that were nonsense in the PSEN2 gene. These two mutations were detected in affected individuals but was absent in controls. These results indicate that PSEN2 mutations may be associated with minority of patients with Alzheimer's disease of Japanese origin.
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Research Products
(12 results)
