| Project/Area Number |
20390248
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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 | Tokyo Metropolitan Institute of Gerontology |
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Principal Investigator |
MURAYAMA Shigeo Tokyo Metropolitan Institute of Gerontology, 東京都健康長寿医療センター研究所, 研究部長 (50183653)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Yuko 独立行政法人国立精神・神経医療研究センター, 臨床検査部, 室長 (60344066)
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| Co-Investigator(Renkei-kenkyūsha) |
ISHII Kenji 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (10231135)
HATSUTA Hiroyuki 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (60469963)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2008: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
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| Keywords | αシヌクレイン / タウ / βアミロイド / パーキンソン病 / レビー小体型認知症 / PIB PET / MRI / ドーパミン / アミロイドβ蛋白 / レビー小体 / 老人班 / 神経原線維変化 / 11C-PIB PET / バーチュアルスライド |
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| Research Abstract |
We studied to identify anatomic substrates to explain dementia in Lewy body disease. Neuropathologically, consecutive autopsy cases were immunocytochemically studied for difference in Lewy body dementia (dementia with Lewy bodies : DLB and Parkinson disease with dementia) Parkinson disease without dementia. Neuroradiologically, PET scans for dopamine transporter (^<11>C-CFT), glucose metabolism (^<18>F-FDG) and amyloid (^<11>C-PIB) were comparatively examined.
Overall, 99 autopsy cases with diagnosis DLB, PDD or PD were recruited for this study. All the cases were immunocytochemically screened for anti-Abta (11-28), phosphorylated tau (AT8) and phosphorylated alpha-synuclein (psyn#64). From 2008-2010, three more autopsy cases were newly recruited for this study. Substrates of DLB/PDD-PD consisted of neocortical plaque as well as alpha-sunuclein deposition in neocortex, limbic system and caudate nucleus. Substrates of Lewy body dementia with neocortical amyloid positive and negative case
… More
s consisted of limbic and necortical alpha-synuclein but not striatal alpha-synuclein. Twenty three cases of pure Lewy body dementia with sufficient alpha-synuclein deposition without significant Abeta and tau deposition were selected from consecutive 8344 autopsy cases and 20 were classified into limbic form and 3 into neocortical form. These pure Lewy body cases lacked striatal Abeta deposition.
About clinical PET studies, three each of DLB/PDD and PD cases were recruited for the study. Decreased ^<11>C-CFT uptake in caudate nucleus of DLB/PDD patients were confirmed. About ^<11>C-PIB PET scans, the three PD cases lacked cortical uptake at all and two out of three PDD/DLB cases also lacked cortical uptake. Thus, the correlation between striatal ^<11>C-CFT uptake and ^<11>C-PIB could not be calculated.
Our data confirmed anatomical substrate for dementia in Lewy body disease consisted of deposition of alpha-synuclein in limbic and neocortical structure. Our study also highlighted deposition of alpha-synuclein in caudate nucleus as strategic target for Lewy body dementia Our study could not confirm the previous reports that striatal deposition of Abeta is responsible for Lewy body dementia.
Pathogenesis of alpha-synuclein deposition and decreased DAT scan in caudate nucleus in Lewy body dementia is yet to be clarified. Less
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