2005 Fiscal Year Final Research Report Summary
A study on the early pathogenic process of Alzheimer's disease by the analysis of the aged V642I-APP knock-in mice brain
| Project/Area Number |
16590846
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Keio University |
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Principal Investigator |
KOUYAMA Keisuke Keio University, School of Medicine, Assistant Prof., 医学部, 講師 (30296553)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Alzheimer's disease / Disease model animals / Amyloid precursor protein / Cerebrum / Gene expression profiling / Early pathogenetic mechanism |
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| Research Abstract |
The 26-28 months old V642I-APP knock-in heterozygous mutant mice, a novel familial Alzheimer's disease (AD) model (Eur J Neurosci.19:2826), showed elevated Aβ1-42/Aβ1-40 ratio in cerebrum homogenates, which is typically observed in patients diagnosed as AD. Performance for the behavioral tests related to memory and learning functions was significantly deteriorated at this age, without apparent formation of senile plaques, neurofibrillary tangles, or massive loss of neurons in cerebrum. Aged heterozygous mutants may therefore reflect the early pathogenetic molecular processes of human AD. Based upon this hypothesis, the quantitative and/or qualitative alteration in gene expression profiles in cerebrum of the aged mice was investigated. Differential display (DD) analysis of the pooled brain samples (four groups : n=5 for mutants and wild types, male and female) detected 207 DD-PCR products, among which 18 showed altered amplification. Differential expression of the 3 independent candidates was confirmed by semi-quantitative PCR analysis and Northern analysis. Analysis of the same brain samples by cDNA subtraction revealed a series of differentially expressed gene candidates, with 6 of which the real-time PCR quantitative analysis confirmed the alteration in gene expression in a V642I-APP mutation-dependent manner. These genes were additionally analyzed for the two sibling pairs of 29 month-old V642I-APP heterozygous mutants and wild type littermates by real-time PCR, which confirmed the nature of the differential expression particularly in cerebral cortex.
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Research Products
(4 results)
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[Journal Article] A humanin derivative, S14G-HN, prevents amyloid-beta-induced memory impairment in mice.2005
Author(s)
Tajima H, Kawasumi M, Chiba T, Yamada M, Yamashita K, Nawa M, Kita Y, Kouyama K, Aiso S, Matsuoka M, Niikura T, Nishimoto I.
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Journal Title
J Neurosci Res. 79(5)
Pages: 714-723
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Targeted introduction of V642I mutation in amyloid precursor protein gene causes functional abnormality resembling early stage of Alzheimer's disease in aged mice.2004
Author(s)
Kawasumi M, Chiba T, Yamada M, Miyamae-Kaneko M, Matsuoka M, Nakahara J, Tomita T, Iwatsubo T, Kato S, Aiso S, Nishimoto I, Kouyama K
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Journal Title
Eur J Neurosci. 19(10)
Pages: 2826-2838
Description
「研究成果報告書概要(欧文)」より
