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Background

Emerging evidence indicates that sleep disorders are the common non-cognitive symptoms of Alzheimer's disease (AD), and they may contribute to the pathogenesis of this disease.

Objective

In this study, we aim to investigate the effect of chronic sleep deprivation (CSD) on AD-related pathologies with a focus on tau phosphorylation and the underlying DNA methylation regulation.

Methods

AβPPswe/PS1ΔE9 AD mice and their wild-type (WT) littermates were subjected to a two-month CSD followed by electroencephalography and electromyography recording. The mice were examined for learning and memory evaluation, then pathological, biochemical, and epigenetic assessments including western blotting, immunofluorescence, dot blotting, and bisulfite sequencing.

Results

The results show that CSD caused sleep disturbances shown as sleep pattern change, poor sleep maintenance, and increased sleep fragmentation. CSD increased tau phosphorylation at different sites and increased the level of tau kinases in AD and WT mice. The increased expression of cyclin-dependent kinase 5 (CDK5) may result from decreased DNA methylation of CpG sites in the promoter region of CDK5 gene, which might be associated with the downregulation of DNA methyltransferase 3A and 3B.

Conclusion

CSD altered AD-related tau phosphorylation through epigenetic modification of tau kinase gene. The findings in this study may give insights into the mechanisms underlying the effects of sleep disturbances on AD pathology and provide new therapeutic targets for the treatment of this disease."xsd:string
http://purl.uniprot.org/citations/37038814http://purl.org/dc/terms/identifier"doi:10.3233/jad-221048"xsd:string
http://purl.uniprot.org/citations/37038814http://purl.uniprot.org/core/author"Li S."xsd:string
http://purl.uniprot.org/citations/37038814http://purl.uniprot.org/core/author"Niu L."xsd:string
http://purl.uniprot.org/citations/37038814http://purl.uniprot.org/core/author"Zhang F."xsd:string
http://purl.uniprot.org/citations/37038814http://purl.uniprot.org/core/author"Zhong R."xsd:string
http://purl.uniprot.org/citations/37038814http://purl.uniprot.org/core/author"Le W."xsd:string
http://purl.uniprot.org/citations/37038814http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37038814http://purl.uniprot.org/core/name"J Alzheimers Dis"xsd:string
http://purl.uniprot.org/citations/37038814http://purl.uniprot.org/core/pages"1341-1355"xsd:string
http://purl.uniprot.org/citations/37038814http://purl.uniprot.org/core/title"Chronic Sleep Disturbances Alters Sleep Structure and Tau Phosphorylation in AbetaPP/PS1 AD Mice and Their Wild-Type Littermates."xsd:string
http://purl.uniprot.org/citations/37038814http://purl.uniprot.org/core/volume"92"xsd:string
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