Microglia and complement mediate early corticostriatal synapse loss and cognitive dysfunction in Huntington's disease.

ABSTRACT: Huntington's disease (HD) is a devastating monogenic neurodegenerative disease characterized by early, selective pathology in the basal ganglia despite the ubiquitous expression of mutant huntingtin. The molecular mechanisms underlying this region-specific neuronal degeneration and how these relate to the development of early cognitive phenotypes are poorly understood. Here we show that there is selective loss of synaptic connections between the cortex and striatum in postmortem tissue from patients with HD that is associated with the increased activation and localization of complement proteins, innate immune molecules, to these synaptic elements. We also found that levels of these secreted innate immune molecules are elevated in the cerebrospinal fluid of premanifest HD patients and corre

SUBMITTER: Wilton DK 

PROVIDER: S-EPMC10667107 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature