Contribution of Neurons and Glial Cells to Complement-Mediated Synapse Removal during Development, Aging and in Alzheimer’s Disease

Synapse loss is an early manifestation of pathology in Alzheimer's disease (AD) and is currently the best correlate to cognitive decline. Microglial cells are involved in synapse pruning during development via the complement pathway. Moreover, recent evidence points towards a key role played by glial cells in synapse loss during AD. However, further contribution of glial cells and the role of neurons to synapse pathology in AD remain not well understood. This review is aimed at comprehensively reporting the source and/or cellular localization in the CNS-in microglia, astrocytes, or neurons-of the triggering components (C1q, C3) of the classical complement pathway involved in synapse pruning in development, adulthood, and AD.The authors thank Dr. Baleriola at Achucarro Basque Center for Neuroscience (Bilbao, Spain) and Dr. Sole-Domenech and Dr. Pipalia at Weill Cornell Medical College (Cornell University, New York, USA) for the helpful and critical revision of the manuscript. This study was supported by CIBERNED and by grants from Ministerio de Economia y Competitividad (SAF2016-75292-R), Gobierno Vasco (PIBA PI-2016-1-009-0016 and ELKARTEK 2016-00033), Ikerbasque, Basque Foundation for Science, and Universidad del Pais Vasco/Euskal Herriko Unibertsitatea UPV/EHU. Jone Zuazo held a fellowship from Gobierno Vasco and Celia Luchena from Fundacion Tatiana Perez de Guzman el Bueno