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Sex moderates apolipoprotein E ε4 effects on sleep expression and memory retention

Sattari Barabadi, N.; Dave, A.; Chen, I. Y.; Kui, K. K.; Chappel-Farley, M. G.; Berisha, D. E.; Sprecher, K. E.; Riedner, b. A.; Jones, S.; Bendlin, B. B.; Mander, B. A.; Benca, R. M.

2026-04-18 pathology
10.64898/2026.04.16.26351049 medRxiv
Show abstract

Introduction: Sleep-dependent memory consolidation differs by sex and maybe disrupted by Alzheimer disease (AD) risk. Whether sex moderates associations between apolipoprotein E {varepsilon}4(APOE {varepsilon}4) status, non-rapid eye movement (NREM) sleep, and memory remains unclear. Methods: Eighty cognitively unimpaired older adults completed a word-pair memory task with encoding and immediate testing occurring prior to overnight polysomnography with high-density electroencephalography (hdEEG) and delayed recall occurring after sleep. Sleep-memory associations were examined as a function of sex and APOE {varepsilon}4 status. Results: In this sample, a sex by APOE {varepsilon}4 interaction was associated with overnight memory retention, with female carriers exhibiting less overnight forgetting than female non-carriers and male {varepsilon}4 carriers. NREM sleep differed by sex and APOE {varepsilon}4 status and was associated with memory retention in {varepsilon}4 carriers. Discussion: These findings indicate sex-specific, sleep-dependent memory mechanisms associated with genetic AD risk, highlighting sleep as a potential early target for intervention, pending replication in larger samples. This study was not a clinical trial.

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