Clinical detection of the earliest pathology in neurite for early specific diagnosis

2016 Fiscal Year Final Research Report

• Project/Area Number: 25430057
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• 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)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: MIBG / 3 リピートタウ

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.

Free Research Field

臨床神経学