TitleBrain cellular senescence in mouse models of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2022
AuthorsDorigatti AO, Riordan R, Yu Z, Ross G, Wang R, Reynolds-Lallement N, Magnusson K, Galvan V, Perez VI
Date Published2022 Apr
KeywordsAlzheimer Disease, Animals, Brain, Cellular Senescence, Disease Models, Animal, Mice, Mice, Transgenic, tau Proteins, Tauopathies

The accumulation of senescent cells contributes to aging pathologies, including neurodegenerative diseases, and its selective removal improves physiological and cognitive function in wild-type mice as well as in Alzheimer's disease (AD) models. AD models recapitulate some, but not all components of disease and do so at different rates. Whether brain cellular senescence is recapitulated in some or all AD models and whether the emergence of cellular senescence in AD mouse models occurs before or after the expected onset of AD-like cognitive deficits in these models are not yet known. The goal of this study was to identify mouse models of AD and AD-related dementias that develop measurable markers of cellular senescence in brain and thus may be useful to study the role of cellular senescence in these conditions. We measured the levels of cellular senescence markers in the brains of P301S(PS19), P301L, hTau, and 3xTg-AD mice that model amyloidopathy and/or tauopathy in AD and related dementias and in wild-type, age-matched control mice for each strain. Expression of cellular senescence markers in brains of transgenic P301L and 3xTg-AD mice was largely indistinguishable from that in WT control age-matched mice. In contrast, markers of cellular senescence were differentially increased in brains of transgenic hTau and P301S(PS19) mice as compared to WT control mice before the onset of AD-like cognitive deficits. Taken together, our data suggest that P301S(PS19) and hTau mice may be useful models for the study of brain cellular senescence in tauopathies including, but not limited to, AD.

Alternate JournalGeroscience
PubMed ID35249206
PubMed Central IDPMC9135905
Grant ListT32 AG021890 / AG / NIA NIH HHS / United States
RF1 AG057964 / AG / NIA NIH HHS / United States
UL1TR002645 / TR / NCATS NIH HHS / United States
RF1 AG068283 / AG / NIA NIH HHS / United States
UL1 TR002645 / TR / NCATS NIH HHS / United States
T32AG021890 / AG / NIA NIH HHS / United States