TY - JOUR
T1 - Tau filaments from amyotrophic lateral sclerosis/parkinsonism-dementia complex adopt the CTE fold
AU - Qi, Chao
AU - Verheijen, Bert M.
AU - Kokubo, Yasumasa
AU - Shi, Yang
AU - Tetter, Stephan
AU - Murzin, Alexey G.
AU - Nakahara, Asa
AU - Morimoto, Satoru
AU - Vermulst, Marc
AU - Sasaki, Ryogen
AU - Aronica, Eleonora
AU - Hirokawa, Yoshifumi
AU - Oyanagi, Kiyomitsu
AU - Kakita, Akiyoshi
AU - Ryskeldi-Falcon, Benjamin
AU - Yoshida, Mari
AU - Hasegawa, Masato
AU - Scheres, Sjors H. W.
AU - Goedert, Michel
PY - 2023
Y1 - 2023
N2 - The amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of the island of Guam and the Kii peninsula of Japan is a fatal neurodegenerative disease of unknown cause that is characterized by the presence of abundant filamentous tau inclusions in brains and spinal cords. Here, we used electron cryo-microscopy to determine the structures of tau filaments from the cerebral cortex of three cases of ALS/PDC from Guam and eight cases from Kii, as well as from the spinal cord of two of the Guam cases. Tau filaments had the chronic traumatic encephalopathy (CTE) fold, with variable amounts of Type I and Type II filaments. Paired helical tau filaments were also found in three Kii cases and tau filaments with the corticobasal degeneration fold in one Kii case. We identified a new Type III CTE tau filament, where protofilaments pack against each other in an antiparallel fashion. ALS/PDC is the third known tauopathy with CTE-type filaments and abundant tau inclusions in cortical layers II/III, the others being CTE and subacute sclerosing panencephalitis. Because these tauopathies are believed to have environmental causes, our findings support the hypothesis that ALS/PDC is caused by exogenous factors.
AB - The amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of the island of Guam and the Kii peninsula of Japan is a fatal neurodegenerative disease of unknown cause that is characterized by the presence of abundant filamentous tau inclusions in brains and spinal cords. Here, we used electron cryo-microscopy to determine the structures of tau filaments from the cerebral cortex of three cases of ALS/PDC from Guam and eight cases from Kii, as well as from the spinal cord of two of the Guam cases. Tau filaments had the chronic traumatic encephalopathy (CTE) fold, with variable amounts of Type I and Type II filaments. Paired helical tau filaments were also found in three Kii cases and tau filaments with the corticobasal degeneration fold in one Kii case. We identified a new Type III CTE tau filament, where protofilaments pack against each other in an antiparallel fashion. ALS/PDC is the third known tauopathy with CTE-type filaments and abundant tau inclusions in cortical layers II/III, the others being CTE and subacute sclerosing panencephalitis. Because these tauopathies are believed to have environmental causes, our findings support the hypothesis that ALS/PDC is caused by exogenous factors.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85179356830&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/38100415
U2 - 10.1073/pnas.2306767120
DO - 10.1073/pnas.2306767120
M3 - Article
C2 - 38100415
SN - 0027-8424
VL - 120
JO - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
IS - 51
M1 - e2306767120
ER -