Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration and myelin deficits
| Autor: | Nicole Koutsodendris, Jessica Blumenfeld, Ayushi Agrawal, Michela Traglia, Brian Grone, Misha Zilberter, Oscar Yip, Antara Rao, Maxine R. Nelson, Yanxia Hao, Reuben Thomas, Seo Yeon Yoon, Patrick Arriola, Yadong Huang |
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| Rok vydání: | 2023 |
| Předmět: |
Neurons
Aging Apolipoprotein E4 Neuroscience (miscellaneous) Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Neurodegenerative Diseases Neurodegenerative Alzheimer's Disease Brain Disorders Mice Tauopathies Neurological Acquired Cognitive Impairment Genetics Animals 2.1 Biological and endogenous factors Dementia Gliosis Geriatrics and Gerontology Aetiology Myelin Sheath |
| Zdroj: | Nature aging, vol 3, iss 3 |
| Popis: | Apolipoprotein E4 (APOE4) is the strongest known genetic risk factor for late-onset Alzheimer’s disease (AD). Conditions of stress or injury induce APOE expression within neurons, but the role of neuronal APOE4 in AD pathogenesis is still unclear. Here we report the characterization of neuronal APOE4 effects on AD-related pathologies in an APOE4-expressing tauopathy mouse model. The selective genetic removal of APOE4 from neurons led to a significant reduction in tau pathology, gliosis, neurodegeneration, neuronal hyperexcitability and myelin deficits. Single-nucleus RNA-sequencing revealed that the removal of neuronal APOE4 greatly diminished neurodegenerative disease-associated subpopulations of neurons, oligodendrocytes, astrocytes and microglia whose accumulation correlated to the severity of tau pathology, neurodegeneration and myelin deficits. Thus, neuronal APOE4 plays a central role in promoting the development of major AD pathologies and its removal can mitigate the progressive cellular and tissue alterations occurring in this model of APOE4-driven tauopathy. |
| Databáze: | OpenAIRE |
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