Cell reports · 2022
Absence of microglia promotes diverse pathologies and early lethality in Alzheimer's disease mice.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Kiani Shabestari Sepideh, Morabito Samuel, Danhash Emma Pascal, McQuade Amanda, Sanchez Jessica Ramirez, Miyoshi Emily, Chadarevian Jean Paul, Claes Christel, Coburn Morgan Alexandra, Hasselmann Jonathan, Hidalgo Jorge, Tran Kayla Nhi, Martini Alessandra C, Chang Rothermich Winston, Pascual Jesse, Head Elizabeth, Hume David A, Pridans Clare, Davtyan Hayk, Swarup Vivek, Blurton-Jones Mathew
Аннотация
Microglia are strongly implicated in the development and progression of Alzheimer's disease (AD), yet their impact on pathology and lifespan remains unclear. Here we utilize a CSF1R hypomorphic mouse to generate a model of AD that genetically lacks microglia. The resulting microglial-deficient mice exhibit a profound shift from parenchymal amyloid plaques to cerebral amyloid angiopathy (CAA), which is accompanied by numerous transcriptional changes, greatly increased brain calcification and hemorrhages, and premature lethality. Remarkably, a single injection of wild-type microglia into adult mice repopulates the microglial niche and prevents each of these pathological changes. Taken together, these results indicate the protective functions of microglia in reducing CAA, blood-brain barrier dysfunction, and brain calcification. To further understand the clinical implications of these findings, human AD tissue and iPSC-microglia were examined, providing evidence that microglia phagocytose calcium crystals, and this process is impaired by loss of the AD risk gene, TREM2.