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[220722 저널발표] Absence of microglia promotes diverse pathologies and early lethality in Alzheimer’s disease mice

한종원 │ 2022-07-20

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2022 Jun 14;39(11):110961.
 doi: 10.1016/j.celrep.2022.110961.

Absence of microglia promotes diverse pathologies and early lethality in Alzheimer's disease mice

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Free PMC article

Abstract

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.

Keywords: Alzheimer’s disease; Alzheimer’s disease co-pathologies; CP: Neuroscience; TREM2; brain calcification; cerebral amyloid angiopathy; hemorrhage; iPSC-microglia; microglia; mortality; neurovascular.




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