A quantitative study of regional accentuation of neurofibrillary degeneration in familial and non-familial Alzheimer's disease
| Project/Area Number |
13670995
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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 |
Psychiatric science
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| Research Institution | Fukui Medical University |
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Principal Investigator |
SUGIMOTO Takahito (2002) Fukui Medical University, Faculty of Medicine, Research Associate, 医学部, 助手 (20334823)
福谷 祐賢 (2001) 福井医科大学, 医学部, 助教授 (10273004)
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| Co-Investigator(Kenkyū-buntansha) |
佐々木 一夫 福井医科大学, 医学部・付属病院, 助手 (50262621)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | Alzheimer's disease / Neurofibrillary degeneration / Hippocampus / Morphometry / APP mutation / PS-1 mutation / Apolipoprotein E / cornu ammonis / Alzheimer's disease / Neurofibrillary pathology / Senile plaque / Hippocampus / Morphometry / Apolipoprotein E |
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| Research Abstract |
Mutations on amyloid β precursor protein (APP) gene and presenilin (PS)-1 gene in familial Alzheimer's disease (AD) and apolipoprotein E (Apo-E) e4 (E4) allele in non-familial AD are presently being recognized as an important risk factor for AD. The hippocampal cortex is constantly affected by neurofibrillary tangles (NFT) in both familial and non-familial AD, but any correlation of genotype with phenotype is still unclear. The purpose of this study was to investigate quantifiable regional accentuation of the density of NFT-free neurons, intracellular NFT (I-NFT), extracellular NFT (e-NFT) and total NFT (I-NFT plus e-NFT) in the hippocampal cortex. Thirteen cases of familial AD including 6 cases with APP717 mutation and 7 with PS-1 mutation, 33 cases of Apo-E genotype-verified non-familial AD and 6 control cases served as the subjects of the present study. The hippocampal cortex was divided into five subdivisions that included the sectors of cornu ammonis (CA) 4, CA3, CA2 and CA1 and t
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he subiculum. The APP717 mutation cases showed more severe neuronal loss and much higher density of e- and total NFT than the non-familial AD cases in sectors CA2 and CA1, while in the subiculum they showed higher NFT-free neuronal density and lower e- and total NFT density than the non-familial AD cases. The PS-1 mutation cases showed more severe neuronal loss and abundant e- and total NFT formation than the non-familial AD cases in the CA sectors, but I-NFT density was not significantly different between these groups. The E4 allele frequency in the non-familial AD cases paralleled the e- and total NFT density in sector CA1 and the subiculum. The duration of disease was inversely correlated with the NFT-free neuron density in sectors CA4 and CA1 and positively correlated with e-NFT density in sector CA1. The neuronal death pattern in sector CA1 paralleled disease progression. Since the duration of the disease between familial AD and non-familial AD was not significantly different, APP717 and PS-1 mutation were thought to modify development of NFT formation in sectors CA2 and CA1 in association with neuronal death in AD. As NFT development in sector CA2 was shown to have no correlation with disease duration or E4 allele frequency in non-familial AD, it may occur only under a limited and specific condition related to APP717 and PS-1 mutation. In addition, PS-1 mutation may accelerate the degeneration from a surviving neuron with NFT into neuronal death via an NFT-dependent pathway, which leads to rapid progression of dementia symptoms with early onset of the disease. Moreover, we also showed in this study that Apo-E E4 is correlated with NFT formation in sector CA1 and the subiculum. Less
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Report
(3 results)
Research Products
(4 results)
