Connections between ApoE, sleep, and Aβ and tau pathologies in Alzheimer’s disease
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 hum...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2023-07-01
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| Series: | The Journal of Clinical Investigation |
| Online Access: | https://doi.org/10.1172/JCI171838 |
| _version_ | 1797634457303252992 |
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| author | Katherine R. Sadleir Robert Vassar |
| author_facet | Katherine R. Sadleir Robert Vassar |
| author_sort | Katherine R. Sadleir |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:08:06Z |
| format | Article |
| id | doaj.art-bda30faeb2444e4091c29e4556298721 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:08:06Z |
| publishDate | 2023-07-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-bda30faeb2444e4091c29e45562987212023-11-07T16:20:38ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-07-0113314Connections between ApoE, sleep, and Aβ and tau pathologies in Alzheimer’s diseaseKatherine R. SadleirRobert VassarIn 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.https://doi.org/10.1172/JCI171838 |
| spellingShingle | Katherine R. Sadleir Robert Vassar Connections between ApoE, sleep, and Aβ and tau pathologies in Alzheimer’s disease The Journal of Clinical Investigation |
| title | Connections between ApoE, sleep, and Aβ and tau pathologies in Alzheimer’s disease |
| title_full | Connections between ApoE, sleep, and Aβ and tau pathologies in Alzheimer’s disease |
| title_fullStr | Connections between ApoE, sleep, and Aβ and tau pathologies in Alzheimer’s disease |
| title_full_unstemmed | Connections between ApoE, sleep, and Aβ and tau pathologies in Alzheimer’s disease |
| title_short | Connections between ApoE, sleep, and Aβ and tau pathologies in Alzheimer’s disease |
| title_sort | connections between apoe sleep and aβ and tau pathologies in alzheimer s disease |
| url | https://doi.org/10.1172/JCI171838 |
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