Cholinergic basal forebrain degeneration due to sleep-disordered breathing exacerbates pathology in a mouse model of Alzheimer’s disease
Issued Date
2022-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-85141167601
Pubmed ID
36323689
Journal Title
Nature Communications
Volume
13
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.13 No.1 (2022)
Suggested Citation
Qian L., Rawashdeh O., Kasas L., Milne M.R., Garner N., Sankorrakul K., Marks N., Dean M.W., Kim P.R., Sharma A., Bellingham M.C., Coulson E.J. Cholinergic basal forebrain degeneration due to sleep-disordered breathing exacerbates pathology in a mouse model of Alzheimer’s disease. Nature Communications Vol.13 No.1 (2022). doi:10.1038/s41467-022-33624-y Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83518
Title
Cholinergic basal forebrain degeneration due to sleep-disordered breathing exacerbates pathology in a mouse model of Alzheimer’s disease
Other Contributor(s)
Abstract
Although epidemiological studies indicate that sleep-disordered breathing (SDB) such as obstructive sleep apnea is a strong risk factor for the development of Alzheimer’s disease (AD), the mechanisms of the risk remain unclear. Here we developed a method of modeling SDB in mice that replicates key features of the human condition: altered breathing during sleep, sleep disruption, moderate hypoxemia, and cognitive impairment. When we induced SDB in a familial AD model, the mice displayed exacerbation of cognitive impairment and the pathological features of AD, including increased levels of amyloid-beta and inflammatory markers, as well as selective degeneration of cholinergic basal forebrain neurons. These pathological features were not induced by chronic hypoxia or sleep disruption alone. Our results also revealed that the cholinergic neurodegeneration was mediated by the accumulation of nuclear hypoxia inducible factor 1 alpha. Furthermore, restoring blood oxygen levels during sleep to prevent hypoxia prevented the pathological changes induced by the SDB. These findings suggest a signaling mechanism whereby SDB induces cholinergic basal forebrain degeneration.