An aging, pathology burden, and glial senescence build-up hypothesis for late onset Alzheimer’s disease

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dc.contributor.authorLau, Victor
dc.contributor.authorRamer, Leanne
dc.contributor.authorTremblay, Marie-Ève
dc.date.accessioned2024-01-25T21:53:55Z
dc.date.available2024-01-25T21:53:55Z
dc.date.copyright2023en_US
dc.date.issued2023
dc.description.abstractAlzheimer’s disease (AD) predominantly occurs as a late onset (LOAD) form involving neurodegeneration and cognitive decline with progressive memory loss. Risk factors that include aging promote accumulation of AD pathologies, such as amyloid-beta and tau aggregates, aswell as inflammation and oxidative stress. Homeostatic glial states regulate and suppress pathology buildup; inflammatory states exacerbate pathology by releasing pro-inflammatory cytokines. Multiple stresses likely induce glial senescence, which could decrease supportive functions and reinforce inflammation. In this perspective, we hypothesize that aging first drives AD pathology burden, whereafter AD pathology putatively induces glial senescence in LOAD. We hypothesize that increasing glial senescence, particularly local senescent microglia accumulation, sustains and drives perpetuating buildup and spread of AD pathologies, glial aging, and further senescence. We predict that increasing glial senescence, particularly local senescent microglia accumulation, also transitions individuals from healthy cognition into mild cognitive impairment and LOAD diagnosis. These pathophysiological underpinnings may centrally contribute to LOAD onset, but require further mechanistic investigation.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipV.Z.L. is supported by a CIHR graduate student award—master and graduate award scholarships from the Faculty of Graduate Studies, University of Victoria. M.E.T. is a Tier II Canada Research Chair in Neurobiology of Aging and Cognition. Both V.Z.L. and M.E.T. are also supported by a CIHR Joint Canada-Israel Health Research Phase II grant.en_US
dc.identifier.citationLau, V., Ramer, L., & Tremblay, M-È. (2023). An aging, pathology burden, and glial senescence build-up hypothesis for late onset Alzheimer's disease. Nature Communications, 14, 1670. https://doi.org/10.1038/s41467-023-37304-3en_US
dc.identifier.urihttps://doi.org/10.1038/s41467-023-37304-3
dc.identifier.urihttp://hdl.handle.net/1828/15883
dc.language.isoenen_US
dc.publisherNature Communicationsen_US
dc.subjectAlzheimer's disease
dc.subjectCognitive ageing
dc.subjectComplexity
dc.subjectMicroglia
dc.subjectNeuroimmunology
dc.subjectInstitute on Aging and Lifelong Health
dc.subjectCentre for Advanced Materials and Related Technology (CAMTEC)
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleAn aging, pathology burden, and glial senescence build-up hypothesis for late onset Alzheimer’s diseaseen_US
dc.typeArticleen_US

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