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Microglia determine beta-amyloid plaque burden but are non-essential for downstream pathology

Li, M.; Holt, K.; Ridley, K.; Qiu, J.; Haddow, K.; Vasoya, D.; He, X.; Tulloch, J.; King, D.; Hume, D. A.; Pridans, C.; Dando, O. R.; Spires-Jones, T. L.; Hardingham, G. E.

2024-08-08 neuroscience
10.1101/2024.08.06.606795 bioRxiv
Show abstract

Evidence points to a role for microglia in Alzheimers disease (AD) risk, although their position in the pathological cascade is incompletely understood, prompting us to generate a model of {beta}-amyloidopathy lacking microglia. We find evidence that microglia promote plaque formation and creation of an A{beta} fibril-rich zone surrounding the plaque core. However, plaque-proximal reactive astrogliosis, synapse loss, and neurite dystrophy are still observed in the absence of microglia.

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