α-synuclein-positive neurites as an early diagnostic indicator

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We traced the Lewy pathology in human brain and demonstrated its initiation at distal axon and subsequent centripetal extension. Expected dysfunction at distal axons, detectable as a decreased myocardial uptake of MIBG, is a reasonable candidate for early and specific diagnosis of Lewy body disease. In contrast, tau deposition start as 4R deposits in dendrites, which may undertake transition to 3R tau with centripetal progression, as we demonstrated with double labeling for 3R/4R tau. We also established a new method to compare light and immunoelectron microscopic findings of the same lesion, which is potentially useful to bridge molecular changes to lesion formation.