Publication Date:
2016-04-02
Description:
Synapse loss in Alzheimer's disease (AD) correlates with cognitive decline. Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease. Here we show in mouse models that complement and microglia mediate synaptic loss early in AD. C1q, the initiating protein of the classical complement cascade, is increased and associated with synapses before overt plaque deposition. Inhibition of C1q, C3, or the microglial complement receptor CR3 reduces the number of phagocytic microglia, as well as the extent of early synapse loss. C1q is necessary for the toxic effects of soluble beta-amyloid (Abeta) oligomers on synapses and hippocampal long-term potentiation. Finally, microglia in adult brains engulf synaptic material in a CR3-dependent process when exposed to soluble Abeta oligomers. Together, these findings suggest that the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hong, Soyon -- Beja-Glasser, Victoria F -- Nfonoyim, Bianca M -- Frouin, Arnaud -- Li, Shaomin -- Ramakrishnan, Saranya -- Merry, Katherine M -- Shi, Qiaoqiao -- Rosenthal, Arnon -- Barres, Ben A -- Lemere, Cynthia A -- Selkoe, Dennis J -- Stevens, Beth -- 1RF1AG051496A/AG/NIA NIH HHS/ -- AG000222/AG/NIA NIH HHS/ -- R01NS083845/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2016 May 6;352(6286):712-6. doi: 10.1126/science.aad8373. Epub 2016 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉F.M. Kirby Neurobiology Center, Boston Children's Hospital (BCH) and Harvard Medical School (HMS), Boston, MA 02115, USA. ; Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital (BWH) and HMS, Boston, MA 02115, USA. ; Alector Inc., 953 Indiana Street, San Francisco, CA 94107, USA. Annexon Biosciences, 280 Utah Avenue Suite 110, South San Francisco, CA 94080, USA. Department of Anatomy, University of California San Francisco (UCSF), San Francisco, CA 94143, USA. ; Department of Neurobiology, Stanford University School of Medicine, Palo Alto, CA 94305, USA. ; Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital (BWH) and HMS, Boston, MA 02115, USA. Prothena Biosciences, Dublin, Ireland. ; F.M. Kirby Neurobiology Center, Boston Children's Hospital (BCH) and Harvard Medical School (HMS), Boston, MA 02115, USA. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. beth.stevens@childrens.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27033548" target="_blank"〉PubMed〈/a〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
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Chemistry and Pharmacology
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Computer Science
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Medicine
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Natural Sciences in General
,
Physics
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