Terminal complement pathway activation drives synaptic loss in Alzheimer's disease models.

ABSTRACT: Complement is involved in developmental synaptic pruning and pathological synapse loss in Alzheimer's disease. It is posited that C1 binding initiates complement activation on synapses; C3 fragments then tag them for microglial phagocytosis. However, the precise mechanisms of complement-mediated synaptic loss remain unclear, and the role of the lytic membrane attack complex (MAC) is unexplored. We here address several knowledge gaps: (i) is complement activated through to MAC at the synapse? (ii) does MAC contribute to synaptic loss? (iii) can MAC inhibition prevent synaptic loss? Novel methods were developed and optimised to quantify C1q, C3 fragments and MAC in total and regional brain homogenates and synaptoneurosomes from WT and App^NL-G-F Alzheimer's disease model mouse brai

SUBMITTER: Carpanini SM 

PROVIDER: S-EPMC9258209 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature