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Basic Science and Pathogenesis.

Negin Sattari1, Abhishek Dave1,2, Kitty K Lui3

  • 1Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.

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|December 24, 2025
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Summary
This summary is machine-generated.

Sleep stages impact overnight memory retention in older adults, with effects varying by sex and APOEε4 genotype. These findings highlight how sleep interacts with Alzheimer's disease (AD) biomarkers and sex to influence memory.

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Area of Science:

  • Neuroscience
  • Gerontology
  • Sleep Medicine

Background:

  • Alzheimer's disease (AD) involves tau and amyloid-β (Aβ) pathologies, influenced by sex, aging, and APOE genotype.
  • The role of sleep in memory consolidation and its interplay with these AD risk factors remain incompletely understood.
  • This study investigates how sex, APOEε4 status, and cerebrospinal fluid (CSF) AD biomarkers affect sleep-dependent memory retention in older adults.

Purpose of the Study:

  • To examine the influence of sex, APOEε4 genotype, and CSF AD biomarkers (Aβ42/40, p-tau) on overnight memory retention.
  • To elucidate the relationship between specific sleep stages (N2, N3) and memory consolidation in the context of AD risk factors.
  • To explore how APOEε4 status moderates the association between sleep, AD biomarkers, and memory.

Main Methods:

  • Sixty-six participants from the Wisconsin Registry for Alzheimer's Prevention underwent overnight polysomnography after encoding word pairs.
  • Memory retention was assessed via a morning test, with sleep stages quantified and CSF biomarkers (p-tau, Aβ42/40) measured.
  • Moderated mediation analysis was employed to examine interactions between sleep stages, memory, biomarkers, sex, and APOEε4 status.

Main Results:

  • A significant sex×APOEε4 interaction revealed differential memory forgetting patterns based on sex and ε4 carrier status.
  • Specific sleep stages were linked to memory retention: N3-sleep in female ε4-non-carriers and N2-sleep in male ε4-carriers.
  • N2-sleep negatively predicted p-tau levels, suggesting a protective role, while higher p-tau correlated with lower memory retention. APOEε4 status influenced Aβ42/40 levels, moderated by sleep.
  • APOEε4 status significantly impacts Aβ42/40 levels, with the relationship between N2-sleep and Aβ42/40 being dependent on APOEε4 carrier status.

Conclusions:

  • NREM sleep stages significantly influence overnight memory retention in older adults, with effects modulated by sex and APOE genotype.
  • Sex differences in long-term memory are shaped by complex interactions between sleep patterns and Alzheimer's disease pathology.
  • These findings underscore the importance of considering sleep, sex, and genetic factors in understanding memory decline and AD progression.