한빛사논문
- 조회893
Washington University School of Medicine, 현 Regeneron Pharmaceuticals
Chanung Wang 1, Aishwarya Nambiar 1, Michael R Strickland 1, Choonghee Lee 1, Samira Parhizkar 1, Alec C Moore 1, Erik S Musiek 1, Jason D Ulrich 1, David M Holtzman 1
1Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, United States of America.
Corresponding Author: David M. Holtzman
Abstract
Alzheimer's disease (AD) is the most common cause of dementia. The APOE-ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD. APOE genotype modulates the effect of sleep disruption on AD risk, suggesting a possible link between apoE and sleep in AD pathogenesis which is relatively unexplored. We hypothesized that apoE modifies Aβ deposition and Aβ plaque-associated tau seeding and spreading in the form of neuritic plaque (NP)-tau pathology in response to chronic sleep deprivation (SD) in an apoE isoform-dependent fashion. To test this hypothesis, we used APPPS1 mice expressing human APOE-ε3 or -ε4 with or without AD-tau injection. We found that SD in APPPS1 mice significantly increased Aβ deposition and peri-plaque NP-tau pathology in the presence of APOE4, but not APOE3. SD in APPPS1 mice significantly decreased microglial clustering around plaques and aquaporin-4 (AQP4) polarization around blood vessels in the presence of APOE4 but not APOE3. We also found that sleep deprived APPPS1:E4 mice injected with AD tau had significantly altered sleep behaviors as compared to APPPS1:E3 mice. These findings suggest that APOE-ε4 genotype is a critical modifier in the development of AD pathology in response to SD.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-06-14)
- 국외 연구진
- 의약학 > 신경의학
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