Altered synaptic ingestion by human microglia in Alzheimer's disease
Michael J.D. Daniels,
Rebecca K Holloway,
Anna J Stevenson,
Veronique E. Miron,
Barry W McColl,
Posted 07 Oct 2019
bioRxiv DOI: 10.1101/795930
Posted 07 Oct 2019
Synapse loss correlates strongly with cognitive decline in Alzheimer's disease, but the mechanisms underpinning this phenomenon remain unclear. Recent evidence from mouse models points to microglial cells as mediators of synapse removal, and human genetic evidence implicates microglia in disease risk. Here we demonstrate that microglia from human post-mortem brain contain synaptic proteins and that greater amounts are observed in microglia from Alzheimer's compared to non-diseased brain tissue. Further, we observe that primary human adult microglia phagocytose synapses isolated from human brain, and that AD brain-derived synapses are phagocytosed more rapidly and abundantly than controls. Together, these data show that synapses in the human AD brain are more prone to ingestion by microglia. Our findings provide evidence from human tissue implicating altered microglial-mediated synaptic uptake in AD pathobiology.
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