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Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer's disease via MFG-E8.
Tzioras, Makis; Daniels, Michael J D; Davies, Caitlin; Baxter, Paul; King, Declan; McKay, Sean; Varga, Balazs; Popovic, Karla; Hernandez, Madison; Stevenson, Anna J; Barrington, Jack; Drinkwater, Elizabeth; Borella, Julia; Holloway, Rebecca K; Tulloch, Jane; Moss, Jonathan; Latta, Clare; Kandasamy, Jothy; Sokol, Drahoslav; Smith, Colin; Miron, Veronique E; Káradóttir, Ragnhildur Thóra; Hardingham, Giles E; Henstridge, Christopher M; Brennan, Paul M; McColl, Barry W; Spires-Jones, Tara L.
Afiliación
  • Tzioras M; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Daniels MJD; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Davies C; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Baxter P; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • King D; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • McKay S; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Varga B; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
  • Popovic K; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Hernandez M; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Stevenson AJ; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Barrington J; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Drinkwater E; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Borella J; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Holloway RK; MRC Centre for Reproductive Health, the University of Edinburgh, Edinburgh EH16 4TJ, UK.
  • Tulloch J; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Moss J; MRC Centre for Reproductive Health, the University of Edinburgh, Edinburgh EH16 4TJ, UK; The Roslin Institute, the Royal (Dick) School of Veterinary Studies, the University of Edinburgh, Edinburgh EH25 9RG, UK.
  • Latta C; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Kandasamy J; Department of Clinical Neurosciences, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.
  • Sokol D; Department of Clinical Neurosciences, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.
  • Smith C; Centre for Clinical Brain Sciences, the University of Edinburgh, Edinburgh EH16 4SB, UK.
  • Miron VE; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; MRC Centre for Reproductive Health, the University of Edinburgh, Edinburgh EH16 4TJ, UK; Barlo Multiple Sclerosis Centre at St. Michael's Hospital, Keenan Research Centre for Biomedical Science, Toronto, ON M5B 1T8,
  • Káradóttir RT; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
  • Hardingham GE; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Henstridge CM; Division of Systems Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UK.
  • Brennan PM; Department of Clinical Neurosciences, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK; Centre for Clinical Brain Sciences, the University of Edinburgh, Edinburgh EH16 4SB, UK.
  • McColl BW; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK. Electronic address: barry.mccoll@ed.ac.uk.
  • Spires-Jones TL; UK Dementia Research Institute, the University of Edinburgh, Edinburgh EH8 9JZ, UK; Centre for Discovery Brain Sciences, the University of Edinburgh, Edinburgh EH8 9JZ, UK. Electronic address: tara.spires-jones@ed.ac.uk.
Cell Rep Med ; 4(9): 101175, 2023 09 19.
Article en En | MEDLINE | ID: mdl-37652017
Synapse loss correlates with cognitive decline in Alzheimer's disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence for any glial involvement in synapse removal in human AD remains to be established. Here we observe astrocytes and microglia from human brains contain greater amounts of synaptic protein in AD compared with non-disease controls, and that proximity to amyloid-ß plaques and the APOE4 risk gene exacerbate this effect. In culture, mouse and human astrocytes and primary mouse and human microglia phagocytose AD patient-derived synapses more than synapses from controls. Inhibiting interactions of MFG-E8 rescues the elevated engulfment of AD synapses by astrocytes and microglia without affecting control synapse uptake. Thus, AD promotes increased synapse ingestion by human glial cells at least in part via an MFG-E8 opsonophagocytic mechanism with potential for targeted therapeutic manipulation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microglía / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: Cell Rep Med Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microglía / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: Cell Rep Med Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos