Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D. & Crowther, R. A. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron 3, 519–524 (1989).

Article  CAS  PubMed  Google Scholar 

Scheres, S. H. W., Ryskeldi-Falcon, B. & Goedert, M. Molecular pathology of neurodegenerative diseases by cryo-EM of amyloids. Nature 621, 701–710 (2023).

Article  CAS  PubMed  Google Scholar 

Schweighauser, M. et al. Mutation ΔK281 in MAPT causes Pick’s disease. Acta Neuropathol. 146, 211–226 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi, Y. et al. Structure-based classification of tauopathies. Nature 598, 359–363 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

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).

Article  PubMed  Google Scholar 

Poorkaj, P. et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43, 815–825 (1998).

Article  CAS  PubMed  Google Scholar 

Hutton, M. et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702–705 (1998).

Article  CAS  PubMed  Google Scholar 

Bugiani, O. et al. Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau. J. Neuropathol. Exp. Neurol. 58, 667–677 (1999).

Article  CAS  PubMed  Google Scholar 

Erro, M. E. et al. Globular glial tauopathy caused by MAPT P301T mutation: clinical and neuropathological findings. J. Neurol. 266, 2396–2405 (2019).

Article  CAS  PubMed  Google Scholar 

Ghetti, B. et al. Frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging. Neuropathol. Appl. Neurobiol. 41, 24–46 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Borrego-Écija, S. et al. Frontotemporal dementia caused by the P301L mutation in the MAPT gene: clinicopathological features of 13 cases from the same geographical origin in Barcelona, Spain. Dement. Geriatr. Cogn. Disord. 44, 213–221 (2017).

Google Scholar 

Tacik, P. et al. Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) due to microtubule-associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy. Neuropathol. Appl. Neurobiol. 43, 200–214 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Forrest, S. L. et al. Retiring the term FTDP-17 as MAPT mutations are genetic forms of sporadic frontotemporal tauopathies. Brain 141, 521–534 (2018).

Article  PubMed  Google Scholar 

Ferrer, I. et al. Familial globular glial tauopathy linked to MAPT mutations: molecular neuropathology and seeding capacity of a prototypical mixed neuronal and glial tauopathy. Acta Neuropathol. 139, 735–771 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rizzu, P. et al. Mutation-dependent aggregation of tau protein and its selective depletion from the soluble fraction in brain of P301L FTDP-17 patients. Hum. Mol. Genet. 9, 3075–3082 (2000).

Article  CAS  PubMed  Google Scholar 

Miyasaka, T. et al. Selective deposition of mutant tau in the FTDP-17 brain affected by the P301L mutation. J. Neuropathol. Exp. Neurol. 60, 872–884 (2001).

Article  CAS  PubMed  Google Scholar 

Hasegawa, M., Smith, M. J. & Goedert, M. Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly. FEBS Lett. 437, 207–210 (1998).

Article  CAS  PubMed  Google Scholar 

D’Souza, I. et al. Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements. Proc. Natl Acad. Sci. USA 96, 5598–5603 (1999).

Article  PubMed  PubMed Central  Google Scholar 

Dayanandan, R. et al. Mutations in tau reduce its microtubule binding properties in intact cells and affect its phosphorylation. FEBS Lett. 446, 228–232 (1999).

Article  CAS  PubMed  Google Scholar 

Nacharaju, P. et al. Accelerated filament formation from tau protein with specific FTDP-17 missense mutations. FEBS Lett. 447, 195–199 (1999).

Goedert, M., Jakes, R. & Crowther, R. A. Effects of frontotemporal dementia FTDP-17 mutations on heparin-induced assembly of tau filaments. FEBS Lett. 450, 306–311 (1999).

Article  CAS  PubMed  Google Scholar 

Chen, D. et al. Tau local structure shields an amyloid-forming motif and controls aggregation propensity. Nat. Commun. 10, 24934 (2019).

Google Scholar 

von Bergen, M. et al. Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif 306VQIVYK311 forming β structure. Proc. Natl Acad. Sci. USA 97, 5129–5134 (2000).

Article  Google Scholar 

Aoyagi, H., Hasegawa, M. N. & Tamaoka, A. Fibrillogenic nuclei composed of P301L mutant tau induce elongation of P301L tau but not wild-type tau. J. Biol. Chem. 282, 20309–20318 (2007).

Article  CAS  PubMed  Google Scholar 

Lewis, J. et al. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant P301L tau protein. Nat. Genet. 25, 402–405 (2000).

Article  CAS  PubMed  Google Scholar 

Götz, J., Chen, F., Barmettler, R. & Nitsch, R. M. Tau filament formation in transgenic mice expressing P301L tau. J. Biol. Chem. 276, 529–534 (2001).

Article  PubMed  Google Scholar 

Allen, B. et al. Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J. Neurosci. 22, 9340–9351 (2002).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yoshiyama, Y. et al. Synapse loss and microglial activation precede tangles in a p301S tauopathy mouse model. Neuron 53, 337–351 (2007).

Article  CAS  PubMed  Google Scholar 

Macdonald, J. A. et al. Assembly of transgenic human P301S tau is necessary for neurodegeneration in murine spinal cord. Acta Neuropathol. Commun. 7, 44 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Espay, A. J. & Lees, A. J. Are we entering the ‘Tau-lemaic’ era of Parkinson’s disease? Brain 147, 330–332 (2024).

Article  PubMed  Google Scholar 

Goedert, M. The ordered assembly of tau is the gain-of-toxic function that causes human tauopathies. Alzheimers Dement. 12, 1040–1050 (2016).

Article  PubMed  Google Scholar 

Schweighauser, M. et al. Cryo-EM structures of tau filaments from the brains of mice transgenic for human mutant P301S tau. Acta Neuropathol. Commun. 11, 160 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao, W. et al. Cryo-EM structures reveal variant tau amyloid fibrils between the rTg4510 mouse model and sporadic human tauopathies. Cell Discov. 10, 27 (2024).

Article  CAS  PubMed  PubMed Central