The mechanisms of low prevalence of senile dementia in patients with leprosy
| Project/Area Number |
09670683
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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 | National Institute of Infectious Diseases |
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Principal Investigator |
ENDOH Masumi Leprosy Research Center, National Institute of Infectious Diseases, Senior Researcher, ハンセン病研究センター・生体防御部, 主任研究官 (20260325)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | leprosy / Senile dementia / Apolipoprotein E / β-amyloid protein / Neurotoxicity / Mycobacterium leprae / βーアミロイド蛋白 / アポトーシス / α1-アンチキモトリプシン |
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| Research Abstract |
A recent epidemiological study indicated that elderly Japanese patients with leprosy had a low prevalence of senile dementia of Alzheimer type (SDAT). In our previous study, elderly patients with leprosy have a low prevalence of senile dementia of Alzheimer type. In addition, the frequency of aィイD4^ィエD4-amyloid protein (AaィイD4^ィエD4) deposition was lower in the brain of non-demented patients with leprosy than in controls. Therefore, we studied mechanisms of low prevalence of SDAT in leprosy patients.
Our results were as follows; Anti-leprosy treatment (dapsone, rifampicin, clofazimine, minomycin or ofloxacin) could not be attributed to either the prevalence of dementia in patients with leprosy or AaィイD4^ィエD4-induced neurotoxicity. The frequency of apolipoprotein E (apo E) aィイD4。ィエD44 allele was elevated in non-demented elderly patients with leprosy. aィイD4'ィエD41-Antichymotrypsin and apo E intron 1 enhancer element polymorphism were not associated with the increased frequency of apo EaィイD4
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。ィエD44 allele in patient with leprosy. However, apo E gene transcriptionalregulatory region (apoE-491A/T, -219G/T) polymorphism was associated with prevalence of SDAT in leprosy patients.
In addition to our present studies regarding genetic factors, the reason for the low incidence of senile dementia in leprosy patients and for the low frequency of AaィイD4^ィエD4 deposition in brains of leprosy patients is not yet clear. It is well recognized tht the central nervous system of mammals is isolated from the infection of Mycobacterium leprae (M. leprae), which is the causative agent for leprosy. However, our recent study clarified that the M. leprae gene was detected in the brain of M. leprae-infected mice by PCR (manuscripts in preparation). This evidence indicates that M. leprae (or a fragment) crosses the blood-brain-barrier in leprosy patients and this may lower the prevalence of senile dementia or frequency of AaィイD4^ィエD4 deposition in leprosy patients. Therefore, it is now important to examine the infection of M. leprae in the central nervous system in leprosy patients. Less
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Report
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Research Products
(8 results)
