| Project/Area Number |
12670592
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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 | Okayama University (2001)
Gunma University (2000) |
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Principal Investigator |
SHOJI Mikio Okayama University, Graduate School of Medicine and Dentistory, Associate Professor, 大学院・医歯学総合研究科, 助教授 (60171021)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Etsuro Okayama University, Hospital, Assistant, 医学部・附属病院, 助手 (70219468)
ABE Koji Okayama University, Graduate School of Medicine and Dentistory, Professor, 大学院・医歯学総合研究科, 教授 (20212540)
HARIGAYA Yasuo Gunma University, Medical School, Lecturere, 医学部, 講師 (90165035)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Alzheimer's Disease / Lipoprotein / Aβ / Plasma / Marker / amyloid |
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| Research Abstract |
APPsw transgenic mice continuously expressed 7 times of human APP than that wild mice. Neuritic plaques appeared at 8 months and diffuse plaques appeared at 10 months old. Conformation changes of soluble Aβ into insoluble Aβ occurred at 8 months old. Acceding with Ab accumulation in the Tg brain, the amount of GSF and plasma Ab decreased progressively. Memory disturbance, decreased levels of acetylcholine, neuronal and synaptic loss, accumulation of phosphorylated tau were observed in APPsw Tg mice. Overproduction of mutant APP reproduced brain amylodosis suggesting this mouse model are excellent animal model for studying pathogenesis and development of treatment of Alzheimer's disease.
APPsw and mutant presenilin-1 L286V double transgenic mice markedly accelerated Aβ amyloidosis. Transgenic mice expressing mutant tau R406W showed progressive tau accumulation in the mouse brain. However, this tau transgenic mouse did not induce Aβ amyloidosis. These findings indicated that Aβ amyloidosis is the cardinal step of Alzheimer pathology and thus Aβ amylidosis is the most important target of treatment of Alzheimer's disease.
In plasma of sporadic Alzheimer's disease, levels of lipoprotein free Aβ were increased. These findings were recognized also in the Alzheimer's brain. These findings suggested that physical circumstance to prevent Aβ aggregation is inhibited in the Alzheimer patients.
Using APPsw mice, we evaluated the effects of 1) Aβ42 vaccine, 2) melatonin on brain amyloidosis. We also examined the side effects of Aβ vaccine on the mice model. Both candidate treatments were effective on Aβ amyloid did in the APPsw brain. However, side effects of Aβ42 vaccine suggest that melatonin is the more possible candidate for clinical trial of treatment of Alzheimer 's disease.
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