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Familial natural short sleep mutations reduce Alzheimer pathology in mice.

TitleFamilial natural short sleep mutations reduce Alzheimer pathology in mice.
Publication TypeJournal Article
Year of Publication2022
AuthorsDong Q, Gentry NW, McMahon T, Yamazaki M, Benitez-Rivera L, Wang T, Gan L, Ptáček L, Fu Y-H
JournaliScience
Volume25
Issue4
Pagination103964
Date Published2022 Apr 15
ISSN2589-0042
Abstract

Although numerous studies have demonstrated that poor sleep increases the development of AD, direct evidence elucidating the benefits of good sleep on the AD pathogenesis is lacking. Familial Natural Short Sleepers (FNSS) are genetically wired to have lifelong reduction in nightly sleep duration without evident consequence on cognitive demise, implying that they may have better sleep quality. Here we investigated two FNSS mutations, DEC2-P384R and Npsr1-Y206H, on the development of tau and amyloid pathology in AD-like mouse models. We found that the development of tau pathology is attenuated in the hippocampus of tau mice carrying FNSS mutations. We also found that DEC2-P384R;5XFAD and female Npsr1-Y206H;5XFAD mice exhibit significantly less amyloid plaques than control mice at 6 months of age. Together, these results reveal that these two FNSS alleles are strong genetic modifiers of AD pathology and may confer resilience to the progression of tau pathology and amyloid plaque formation in neurodegeneration.

DOI10.1016/j.isci.2022.103964
Alternate JournaliScience
PubMed ID35496999
PubMed Central IDPMC9042888
Grant ListRF1 AG054606 / AG / NIA NIH HHS / United States