| Project/Area Number |
07457158
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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 | Jichi Medical School Omiya Medical Center |
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Principal Investigator |
UEKI Akira Jichi Medical School, Omiya Medical Center, Department of Neurology, Associate professor, MD, 医学部, 助教授 (90112622)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUTANI Toshio Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Direc, 神経病理部, 部長 (40124416)
OTSUKA Mieko Jichi Medical School, Omiya Medical Center, Department of Neurology, Lecturer, M, 医学部, 講師 (30194210)
池田 和彦 東京都精神医学総合研究所, 超微形態, 副参事 (30124663)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1996: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1995: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Alzheimer's disease / senile dementia / apolipoprotein E / apolipoprotein E-epsilon4 / paraffin section / pathology / ε-4遺伝子型 / 危険因子 / 脳切片 / アポリポ蛋白E-ε4 / 神経病理 |
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| Research Abstract |
PURPOSE : Apolipoprotein E (apoE-epsilon4) is a risk factor of Alzheimer's disease (AD). In this study, we extracted DNAs from paraffin embedded brain tissue in patients with AD and controls, and genotyped apoE and alpha1-antichymotrypsin (ACT) signal peptide polymorphism. We investigated gene dose effect of epsilon4 on the onset age of dementia. SUBJECTS and METHODS : Subjects were consisted of 7 early onset AD (EOAD), 13 late onset AD (LOAD), and 36 controls who died of non-neurological diseases and were not demented before death. DNAs were extracted from 5 paraffin sections (10mu). Genotypes of apoE and ACT were determined by PCR based methods described previously. RESULTS : ApoE was successfully determined in 36 out of 55 samples examined (65.5%). The distribution of apoE genotype in controls were E3/25 (20.8%), E3/3 18 (75.0.0%), E4/3 1 (4.2%). In AD,the E4/3 genotype was overexpressed (E3/3 ; 33.3%, E4/3 ; 66.7%), confirming the previous results. Onset age of dementia in epsilon4 corriers and epsilon4 non-carriers were 65.5(]SY.+-。[)4.9y.o.and 57.9(]SY.+-。[)19.3y.o., respectively, which apparently denying the gene dose effect of epsilon4 on age of onset. However, when samples from EOAD were excluded, the onset age of epsilon4 non-carriers became 72.5(]SY.+-。[)12.5y.o. The ratio of epsilon4-carriers in pathologically verified EOAD and LOAD were 0/3, and 4/9, respectively. The distribution of ACT genotyped were identical in AD and controls. DISCUSSION : The association of apoE and AD is strongly limited to LOAD or senile dementia of Alzheimer's type (SDAT). In contrast to the previous report, ACT genotypes did not show any effect on the risk of AD either independently or dependently to apoE.
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