Reference - Detail
| RRC ID | 87291 |
|---|---|
| Author | AlQot HE, Rylett RJ. |
| Title | Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer's disease-like pathology in the APPNL-G-F knock-in mouse model. |
| Journal | Sci Rep |
| 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 APPNL-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 and gliosis. These effects were inversely related to age and Aβ 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. |
| Volume | 14(1) |
| Pages | 27614 |
| Published | 2024-11-11 |
| DOI | 10.1038/s41598-024-78751-2 |
| PII | 10.1038/s41598-024-78751-2 |
| PMID | 39528509 |
| PMC | PMC11555257 |
| MeSH | Alzheimer Disease* / genetics Alzheimer Disease* / metabolism Alzheimer Disease* / pathology Amyloid beta-Peptides / metabolism Amyloid beta-Protein Precursor / genetics Amyloid beta-Protein Precursor / metabolism Animals Choline O-Acetyltransferase* / genetics Choline O-Acetyltransferase* / metabolism Cognitive Dysfunction / genetics Cognitive Dysfunction / metabolism Cognitive Dysfunction / pathology Disease Models, Animal* Disease Progression Gene Knock-In Techniques Humans Male Mice Mice, Transgenic* Neurons / metabolism Neurons / pathology Plaque, Amyloid / metabolism Plaque, Amyloid / pathology Primates |
| Resource | |
| Mice | RBRC06344 |