Journal article
Mouse and human microglial phenotypes in Alzheimer’s disease are controlled by amyloid plaque phagocytosis through Hif1α
Alexandra Grubman, Xin Yi Choo, Gabriel Chew, John Ouyang, Guizhi Sun, Nathan Croft, Fernando Rossello, Rebecca Simmons, Sam Buckberry, Dulce Vargas Landin, Jahnvi Pflueger, Teresa Vandekolk, Zehra Abay, Xiaodong Liu, John Haynes, Catriona McLean, Sarah Williams, Siew Yeen Chai, Trevor Wilson, Ryan Lister Show all
Published : 2019
DOI: 10.1101/639054
Abstract
ABSTRACT The important role of microglia, the brain’s resident immune cells, in Alzheimer’s disease (AD) is now well recognized, however their molecular and functional diversity and underlying mechanisms still remain controversial. To transcriptionally and functionally characterize the diversity of microglia in AD and aging, we isolated the amyloid plaque-containing (XO4 + ) and non-containing (XO4 − ) microglia from an AD mouse model. Transcriptomics analysis unveiled independent transcriptional trajectories in ageing and AD. XO4 + microglial transcriptomes linked plaque phagocytosis to altered expression of bona fide late onset AD genetic risk factors. We further revealed that the XO4 + tr..
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