Article ; Online: Connections between ApoE, sleep, and Aβ and tau pathologies in Alzheimer's disease.
The Journal of clinical investigation
2023 Volume 133, Issue 14
Abstract: In this issue of the JCI, Wang and colleagues investigate the relationship between sleep disturbances, an environmental risk factor for Alzheimer's disease (AD), and the apolipoprotein 4 (APOEε4) allele, a strong genetic risk factor for AD. The authors ... ...
Abstract | In this issue of the JCI, Wang and colleagues investigate the relationship between sleep disturbances, an environmental risk factor for Alzheimer's disease (AD), and the apolipoprotein 4 (APOEε4) allele, a strong genetic risk factor for AD. The authors subjected an amyloid mouse model expressing human APOE3 or APOE4, with and without human AD-tau injection, to sleep deprivation and observed that amyloid and tau pathologies were worsened in the presence of APOE4. Moreover, decreased microglial clustering and increased dystrophic neurites around plaques were observed in sleep-deprived APOE4 mice. In addition, aquaporin 4, important for clearing amyloid-β through the glymphatic system, was reduced and less polarized to astrocytic endfeet. These APOE4-induced changes caused alterations in sleep behavior during recovery from sleep deprivation, suggesting a feed-forward cycle of sleep disturbance and increased AD pathology that can further disrupt sleep in the presence of APOE4. |
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MeSH term(s) | Animals ; Humans ; Mice ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/genetics ; Apolipoprotein E4/genetics ; Apolipoproteins E ; Mice, Transgenic ; Sleep Deprivation/genetics ; Sleep Deprivation/complications |
Chemical Substances | Amyloid beta-Peptides ; Apolipoprotein E4 ; Apolipoproteins E ; Apoe protein, mouse |
Language | English |
Publishing date | 2023-07-17 |
Publishing country | United States |
Document type | Journal Article ; Comment |
ZDB-ID | 3067-3 |
ISSN | 1558-8238 ; 0021-9738 |
ISSN (online) | 1558-8238 |
ISSN | 0021-9738 |
DOI | 10.1172/JCI171838 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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