Complement-mediated synapse loss in Alzheimer's disease: mechanisms and involvement of risk factors

Trends Neurosci. 2023 Dec 20:S0166-2236(23)00272-2. doi: 10.1016/j.tins.2023.11.010. Online ahead of print.ABSTRACTThe complement system is increasingly recognized as a key player in the synapse loss and cognitive impairments observed in Alzheimer's disease (AD). In particular, the process of complement-dependent synaptic pruning through phagocytosis is over-activated in AD brains, driving detrimental excessive synapse elimination and contributing to synapse loss, which is the strongest neurobiological correlate of cognitive impairments in AD. Herein we review recent advances in characterizing complement-mediated synapse loss in AD, summarize the underlying mechanisms, and discuss the possible involvement of AD risk factors such as aging and various risk genes. We conclude with an overview of key questions that remain to be addressed.PMID:38129195 | DOI:10.1016/j.tins.2023.11.010
Source: Trends in Neurosciences - Category: Neuroscience Authors: Source Type: research