RT Journal Article
SR Electronic
T1 Altered synaptic ingestion by human microglia in Alzheimer’s disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 795930
DO 10.1101/795930
A1 Makis Tzioras
A1 Michael J.D. Daniels
A1 Declan King
A1 Karla Popovic
A1 Rebecca K. Holloway
A1 Anna J. Stevenson
A1 Jane Tulloch
A1 Jothy Kandasamy
A1 Drahoslav Sokol
A1 Clare Latta
A1 Jamie Rose
A1 Colin Smith
A1 Veronique E. Miron
A1 Christopher Henstridge
A1 Barry W. McColl
A1 Tara L. Spires-Jones
YR 2019
UL http://biorxiv.org/content/early/2019/10/07/795930.abstract
AB 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 postmortem 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.One Sentence Summary AD alters synapse ingestion by microglia