Tau filaments with the Alzheimer fold in cases with MAPT mutations V337M and R406W

• Published in: bioRxiv : the preprint server for biology
• Main Authors: Qi, Chao, Lövestam, Sofia, Murzin, Alexey G, Peak-Chew, Sew, Franco, Catarina, Bogdani, Marika, Latimer, Caitlin, Murrell, Jill R, Cullinane, Patrick W, Jaunmuktane, Zane, Bird, Thomas D, Ghetti, Bernardino, Scheres, Sjors H W, Goedert, Michel
• Format: Journal Article
• Language: English
• Published: United States 30.04.2024
• DOI: 10.1101/2024.04.29.591661

Frontotemporal dementia (FTD) and Alzheimer's disease are the most common forms of early-onset dementia. Dominantly inherited mutations in , the microtubule-associated protein tau gene, cause FTD and parkinsonism linked to chromosome 17 (FTDP-17). Individuals with FTDP-17 develop abundant filamentous tau inclusions in brain cells. Here we used electron cryo-microscopy to determine the structures of tau filaments from the brains of individuals with mutations V337M and R406W. Both mutations gave rise to tau filaments with the Alzheimer fold, which consisted of paired helical filaments in all V337M and R406W cases and of straight filaments in two V337M cases. We also identified a new assembly of the Alzheimer fold into triple tau filaments in a V337M case. Filaments assembled from recombinant tau(297-391) with mutation V337M had the Alzheimer fold and showed an increased rate of assembly.