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Mutant tau filaments from some inherited frontotemporal dementias show the Alzheimer fold

Frontotemporal dementias can be caused by mutations in MAPT, which encodes the protein tau; the mutant protein forms harmful aggregates in the brain. Cryo-electron microscopy of tau filaments from individuals with mutant V337M and R406W tau show the Alzheimer fold.

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Fig. 1: Cryo-EM cross sections of filaments.

References

Goedert, M., Crowther, R. A., Scheres, S. H. W. & Spillantini, M. G. Tau and neurodegeneration. Cytoskeleton 81, 95–102 (2024). This review summarizes tau isoforms, assemblies, genetics and structures.

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Schweighauser, M. et al. Novel tau filament folds in individuals with MAPT mutations P301L and P301T. Preprint at bioRxivhttps://doi.org/10.1101/2024.08.15.608062 (2024). This preprint reports that the structures of tau filaments from individuals with MAPT mutations resulting in P301L and P301T tau are unlike those from sporadic and other inherited tauopathies.

Spillantini, M. G., Crowther, R. A. & Goedert, M. Comparison of the neurofibrillary pathology in Alzheimer's disease and familial presenile dementia with tangles. Acta Neuropathol. 92, 42–48 (1996). Tau filaments from individuals with MAPT mutation leading to V337M tau are like those from individuals with AD.

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This is a summary of: Qi, C. et al. Tau filaments with the Alzheimer fold in human MAPT mutants V337M and R406W. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-025-01498-5 (2025).

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Mutant tau filaments from some inherited frontotemporal dementias show the Alzheimer fold. Nat Struct Mol Biol (2025). https://doi.org/10.1038/s41594-025-01499-4

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Published:12 March 2025

DOI:https://doi.org/10.1038/s41594-025-01499-4

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