Microglia function and dysfunction in Alzheimer’s disease │Dr Beth Stevens скачать в хорошем качестве

Microglia function and dysfunction in Alzheimer’s disease │Dr Beth Stevens

Summary: 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, ageing 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. Speaker Bio: 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. Her research is focused on understanding how neural-immune interactions in the brain sculpt synapses during normal development and disease. She and her team discovered that microglia, the brain’s resident immune cells, prune neural connections in response to signals from the classical complement pathway, a branch of the immune system. Her lab has uncovered a diverse set of immune molecules that regulate this process in the brain during normal development, providing insights into the pathological synapse loss of Alzheimer’s disease, dementia, and schizophrenia. She has adopted an interdisciplinary approach that straddles the fields of genetics, immunology, and neuroscience to understand how neural-immune interactions regulate brain wiring, neural circuit function, and behaviour. 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 PhD from the University of Maryland, College Park. She completed her postdoctoral research at Stanford University with Ben Barres. Moderator: Mosab Ali Awadelkareem, Al-Neelain University, Sudan. Society of Neuroscientists of Africa – SONA: https://sonafrica.org/   / sonaorg     / society-of-neuroscientists-of-africa-sona-...      / @societyofneuroscientistsof385   TReND in Africa: https://trendinafrica.org/ https://www.flickr.com/photos/trendin... https://twitter.com/trendinafrica?lan...   / trendinafrica   Worldwide Neuro: https://www.worldwideneuro.com/   / worldwideneuro