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Amyloid fibrils in disease FTLD-TDP are composed of TMEM106B not TDP-43
Yi Xiao Jiang # 1 2, Qin Cao # 1 2 3, Michael R Sawaya 1 2, Romany Abskharon 1 2, Peng Ge 1 2, Michael DeTure 4, Dennis W Dickson 4, Janine Y Fu 1, Rachel R Ogorzalek Loo 1, Joseph A Loo 1, David S Eisenberg 5 6
Abstract:
...Here, we extracted amyloid fibrils from brains of four patients, representing four out of five FTLD-TDP subclasses and determined their near-atomic resolution structures by cryogenic electron-microscopy (cryo-EM). Unexpectedly, all amyloid fibrils examined are composed of a 135-residue C-terminal fragment of transmembrane protein 106B (TMEM106B), a lysosomal membrane protein previously implicated as a genetic risk factor for FTLD-TDP4. In addition to TMEM106B fibrils, abundant non-fibrillar aggregated TDP-43 is present, as revealed by immunogold labeling. Our observations confirm that FTLD-TDP is an amyloid-involved disease and suggest that amyloid involvement in FTLD-TDP is of protein TMEM106B, rather than of TDP-43.
