A novel rhesus macaque model of Huntington's disease recapitulates key neuropathological changes along with motor and cognitive decline.

ABSTRACT: We created a new nonhuman primate model of the genetic neurodegenerative disorder Huntington's disease (HD) by injecting a mixture of recombinant adeno-associated viral vectors, serotypes AAV2 and AAV2.retro, each expressing a fragment of human mutant HTT (mHTT) into the caudate and putamen of adult rhesus macaques. This modeling strategy results in expression of mutant huntingtin protein (mHTT) and aggregate formation in the injected brain regions, as well as dozens of other cortical and subcortical brain regions affected in human HD patients. We queried the disruption of cortico-basal ganglia circuitry for 30 months post-surgery using a variety of behavioral and imaging readouts. Compared to controls, mHTT-treated macaques developed working memory decline and progressive mo

SUBMITTER: Weiss AR 

PROVIDER: S-EPMC9545527 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature