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X-Linked Ubiquitin-Specific Peptidase 11 Increases Tauopathy Vulnerability In Women, Yan Yan
X-Linked Ubiquitin-Specific Peptidase 11 Increases Tauopathy Vulnerability In Women, Yan Yan
USF Tampa Graduate Theses and Dissertations
Women experience significantly higher tau burden and increased risk for Alzheimer’s disease (AD) than men, yet the underlying mechanism for this vulnerability has not been explained. Here, we demonstrate through in vitro and in vivo models, as well as human AD brain tissue, that X-linked ubiquitin specific peptidase 11 (USP11) augments pathological tau aggregation via tau deubiquitination initiated at lysine-281. Removal of ubiquitin provides access for enzymatic tau acetylation at lysines 281 and 274. USP11 escapes complete X-inactivation, and female mice and people both exhibit higher USP11 levels than males. Genetic elimination of usp11 in a tauopathy mouse model preferentially …