TDP-43 Depletion in Microglia Promotes Amyloid Clearance but Also Induces Synapse Loss.

ABSTRACT: Microglia coordinate various functions in the central nervous system ranging from removing synaptic connections, to maintaining brain homeostasis by monitoring neuronal function, and clearing protein aggregates across the lifespan. Here we investigated whether increased microglial phagocytic activity that clears amyloid can also cause pathological synapse loss. We identified TDP-43, a DNA-RNA binding protein encoded by the Tardbp gene, as a strong regulator of microglial phagocytosis. Mice lacking TDP-43 in microglia exhibit reduced amyloid load in a model of Alzheimer's disease (AD) but at the same time display drastic synapse loss, even in the absence of amyloid. Clinical examination from TDP-43 pathology cases reveal a considerably reduced prevalence of AD and decreased amyloid patholog

SUBMITTER: Paolicelli RC 

PROVIDER: S-EPMC5519492 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature