Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer's disease-like pathology in the APP^NL-G-F knock-in mouse model.

ABSTRACT: Alzheimer's disease (AD) is characterized by amyloidosis, neuroinflammation, cholinergic dysfunction and cognitive impairment. In AD, the cholinergic neuronal marker choline acetyltransferase (ChAT) is reduced and the primate-specific nuclear isoform, 82-kDa ChAT, is mislocalized to cytoplasm. Cell-based studies suggest a role for 82-kDa ChAT in regulating expression of AD-related genes with potential reductions in β-amyloid (Aβ) levels. To study this further, we crossed transgenic mice expressing human 82-kDa ChAT with the AD mouse model APP^NL-G-F and used molecular techniques and neurobehavioral tests to study the impact of 82-kDa ChAT on AD pathology. These mice had altered expression of genes linked to Aβ clearance and inflammation, and reduced cognitive decline, amyloidosis

SUBMITTER: AlQot HE 

PROVIDER: S-EPMC11555257 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature