| First Author | AlQot HE | Year | 2024 |
| Journal | Sci Rep | Volume | 14 |
| Issue | 1 | Pages | 27614 |
| PubMed ID | 39528509 | Mgi Jnum | J:358452 |
| Mgi Id | MGI:7780945 | Doi | 10.1038/s41598-024-78751-2 |
| Citation | AlQot HE, et al. (2024) Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer's disease-like pathology in the APP(NL-G-F) knock-in mouse model. Sci Rep 14(1):27614 |
| abstractText | 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 beta-amyloid (Abeta) 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 Abeta clearance and inflammation, and reduced cognitive decline, amyloidosis and gliosis. These effects were inversely related to age and Abeta plaque load and correlated best with 82-kDa ChAT localized to nuclei of neurons. The study suggests a role for 82-kDa ChAT in decreasing AD-like pathology. |
