Clinical detection of the earliest pathology in neurite for early specific diagnosis
| Project/Area Number |
25430057
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
UCHIHARA Toshiki 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 副参事研究員 (10223570)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | MIBG / 3 リピートタウ / MIBG心筋シンチグラフィー / 心筋内軸索 / 4Rタウ / シヌクレイン / Neuromorphomics / 免疫電顕 / 量子ドット / レヴィー小体 / 神経突起病理学 / 軸索 / 心臓交感神経 / αシヌクレイン / パーキンソン病 / レヴィー小体型認知症 |
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| Outline of Final Research Achievements |
Lewy pathology occurs preferentially in systems with hyperbranching axon, where alpha-synuclein deposition occurs in distal axons. Because cardiac sympathetic nerve is affected early in Lewy body disorders, corresponding reduction in myocardial uptake of MIBG suggests the presence of Lewy body. Because Lewy pathology and corresponding clinical manifestations occur in whatever combination and sequence, we propose “Multifocal Lewy body disease” to account for their clinicopathological diversities. Neurofibrillary tangles of AD contain three-repeat and four-repeat tau. 4R tau deposition features early phase followed by replacement with 3R tau. This profile shift is initiated at dendrites and spreads towards neuronal soma. How 3R and 4R tau are related may be fundamental, which we are challenging by performing double-labelling immunoelectron microscopy with a novel technique. Preferential involvement of distal axons in Lewy body is in sharp contrast with dendritic involvement of AD-NFT.
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Report
(5 results)
Research Products
(65 results)
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[Journal Article] Direct quantitative correlation between cardiac MIBG uptake and remaining axons in cardiac sympathethic nerve in Lewy body disease2015
Author(s)
Makoto Takahashi, Masako Ikemura, Teruaki Oka, Toshiki Uchihara, Koichi Wakabayashi, Akiyoshi Kakita, Hitoshi Takahashi, Mari Yoshida, Shuta Toru, Takayoshi Kobayashi, Satoshi Orimo
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Journal Title
Journal of Neurology, Neurosurgery, and Psychiatry
Volume: Online First
Issue: 9
Pages: 939-44
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Lateralized Cortical Involvement and Contralateral Parkinsonism without Basal Ganglia Involvement in Two Autopsy Cases of Corticobasal Syndrome-Alzheimer's Disease2014
Author(s)
Homma, T. Takubo, H. Takahashi, K. Matsubara, S. Takahashi, M. Funata, N. Mochizuki, Y. Mizutani, T. Komori, T. Uchihara, T.
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Journal Title
J Alzheimers Dis
Volume: 40
Issue: 1
Pages: 51-5
DOI
Related Report
Peer Reviewed
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[Presentation] タウ病変のはじまりと変遷2014
Author(s)
内原俊記
Organizer
2014タウミーティング
Place of Presentation
同志社大学東京オフィス（東京都・中央区)
Year and Date
2014-08-01
Related Report
Invited
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