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Tau filaments from amyotrophic lateral sclerosis/parkinsonism-dementia complex adopt the CTE fold.

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Verheijen, Bert M 
Shi, Yang 
Tetter, Stephan 


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.


Peer reviewed: True

Publication status: Published


amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS/PDC), chronic traumatic encephalopathy tau fold, neurodegenerative disease, tau filament assembly, Humans, Amyotrophic Lateral Sclerosis, Dementia, Chronic Traumatic Encephalopathy, Neurodegenerative Diseases, Parkinsonian Disorders, Tauopathies, Japan, tau Proteins

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Proc Natl Acad Sci U S A

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Proceedings of the National Academy of Sciences
UKRI | Medical Research Council (MRC) (MC_UP_A025_1013)
UKRI | Medical Research Council (MRC) (MC_U105184291)
UKRI | Medical Research Council (MRC) (MC_UP_120/25)
HHS | NIH | National Institute on Aging (NIA) (R01AG054641)
the Research Committee on Muro Disease (21210301)
MEXT | Japan Society for the Promotion of Science (JSPS) (JSPS KAKENHI)
MEXT | Japan Society for the Promotion of Science (JSPS) (JP18K07514)
MEXT | Japan Society for the Promotion of Science (JSPS) (JP22H04923)
Swiss National Science Postdoctoral Fellowship (P500PB 206890)