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Microglia function and dysfunction in Alzheimer’s disease
Emerging genetic studies of late-onset Alzheimer’s Disease implicate the brain’s resident macrophages in the pathogenesis of AD. More than half the risk genes associated with late-onset AD are selectively expressed in microglia and peripheral myeloid cells; yet we know little about the underlying biology or how myeloid cells contribute to AD pathogenesis. Using single-cell RNA sequencing and spatial transcriptomics we identified molecular signatures that can be used to localize and monitor distinct microglia functional states in the human and mouse brain. Our results show that microglia assume diverse functional states in development, aging and injury, including populations corresponding to known microglial functions including proliferation, migration, inflammation, and synaptic phagocytosis. We identified several innate immune pathways by which microglia recognize and prune synapses during development and in models of Alzheimer’s disease, including the classical complement cascade. Illuminating the mechanisms by which developing synaptic circuits are sculpted is providing important insight on understanding how to protect synapses in Alzheimer’s and other neurodegenerative diseases of synaptic dysfunction.

Oct 8, 2020 04:00 PM in London

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Beth Stevens
Dr @Harvard Medical School
Beth Stevens is an Associate Professor at Harvard Medical School in the FM Kirby Neurobiology Center at Boston Children’s Hospital, an Institute Member of the Broad Institute and Stanley Center for Psychiatric Research, Howard Hughes Medical Institute Investigator and member of the National Academy of Medicine. Stevens was named a MacArthur Fellow in 2015. She has also shared the National Alliance on Mental Illness (NAMI) Research Award with Steven McCarroll and Michael Carroll in 2016 for their collaborative work on C4 and schizophrenia. Stevens received her B.S. at Northeastern University. She carried out her graduate research at the National Institutes of Health and received her Ph.D. from University of Maryland, College Park. She completed her postdoctoral research at Stanford University with Ben Barres.