Article
A pathogenic Tau mutation drives autophagy-lysosome dysfunction that limits Tau degradation in a model of frontotemporal dementia.
Nature communications - 31 Mar 2026
Mirfakhar Farzaneh S, Marsh Jacob A, Sato Chihiro, Schache Kylie J, Minaya Miguel A, Dolle Roland E, Pak Stephen C, Silverman Gary A, Perlmutter David H, Macauley Shannon L, Karch Celeste M
Abstract excerpt
Tau accumulates in a group of neurodegenerative diseases known as tauopathies. A prevailing hypothesis has been that Tau degradation is impaired due to an age-related imbalance in the autophagy-lysosome pathway, but whether these defects are a cause or consequence of Tau accumulation remains unclear. Here we show that a disease-causing mutation in the MAPT gene, which encodes Tau, p.R406W, is sufficient to...
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