Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer’s disease-like pathology in the APPNL-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 cytopla...
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-78751-2 |
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| author | Hadir E. AlQot Rebecca Jane Rylett |
| author_facet | Hadir E. AlQot Rebecca Jane Rylett |
| author_sort | Hadir E. AlQot |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6a1c4460b13e454b83e19b5852d0dedd |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-6a1c4460b13e454b83e19b5852d0dedd2024-11-17T12:29:43ZengNature PortfolioScientific Reports2045-23222024-11-0114111710.1038/s41598-024-78751-2Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer’s disease-like pathology in the APPNL-G-F knock-in mouse modelHadir E. AlQot0Rebecca Jane Rylett1Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Robarts Research Institute, University of Western OntarioDepartment of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Robarts Research Institute, University of Western OntarioAbstract 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.https://doi.org/10.1038/s41598-024-78751-282-kDa choline acetyltransferaseAPPNL-G-F miceAlzheimer’s diseaseβ-Amyloid clearanceMicrogliaNeurobehavioral testing |
| spellingShingle | Hadir E. AlQot Rebecca Jane Rylett Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer’s disease-like pathology in the APPNL-G-F knock-in mouse model Scientific Reports 82-kDa choline acetyltransferase APPNL-G-F mice Alzheimer’s disease β-Amyloid clearance Microglia Neurobehavioral testing |
| title | Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer’s disease-like pathology in the APPNL-G-F knock-in mouse model |
| title_full | Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer’s disease-like pathology in the APPNL-G-F knock-in mouse model |
| title_fullStr | Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer’s disease-like pathology in the APPNL-G-F knock-in mouse model |
| title_full_unstemmed | Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer’s disease-like pathology in the APPNL-G-F knock-in mouse model |
| title_short | Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer’s disease-like pathology in the APPNL-G-F knock-in mouse model |
| title_sort | primate specific 82 kda choline acetyltransferase attenuates progression of alzheimer s disease like pathology in the appnl g f knock in mouse model |
| topic | 82-kDa choline acetyltransferase APPNL-G-F mice Alzheimer’s disease β-Amyloid clearance Microglia Neurobehavioral testing |
| url | https://doi.org/10.1038/s41598-024-78751-2 |
| work_keys_str_mv | AT hadirealqot primatespecific82kdacholineacetyltransferaseattenuatesprogressionofalzheimersdiseaselikepathologyintheappnlgfknockinmousemodel AT rebeccajanerylett primatespecific82kdacholineacetyltransferaseattenuatesprogressionofalzheimersdiseaselikepathologyintheappnlgfknockinmousemodel |