| Budget Amount *help |
¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2017: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2016: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2015: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000)
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| Outline of Final Research Achievements |
We analyzed pathological tau in various neurodegenerative diseases and found that the C-terminal banding pattern of the insoluble tau is distinct for each disease, suggesting that the band patterns reflect different conformations of tau molecular species. We also showed that extracellular region of APP is involved in uptake of tau fibrils into cells, raising the possibility that APP influences cell-to-cell spreading of tau pathologies in AD. In addition, we identified that residues 274-353 are responsible for the conversion of TDP-43 to amyloid-like fibrils and that templated aggregation of TDP-43 by seeding with different peptides induces various types of TDP-43 pathologies. Regarding alpha-synuclein, we showed that fragmented amyloid-like aggregates of short alpha-synunclein fibrils are the key pathogenic seeds that trigger prion-like conversion, and that the propagation is recapitulated in wild-type marmoset by inoculation of sonicated mouse alpha-synculein fibrils.
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