The Association Between Polygenic Risk for Alzheimer's, Objective Sleep Architecture, and Plasma Neurofilament Light Chain in Midlife

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Published: 2026-01-15
DOI: https://doi.org/10.61919/wyfc0r72
Keywords:
Alzheimer Disease; Genetic Predisposition to Disease; Middle Aged; Neurofilament Proteins; Polysomnography; Sleep, Slow-Wave.

Main Article Content

Asma Riffaqat
Psychologist, University of Peshawar, Peshawar, Pakistan
Sumera Kanwal
Assistant Professor, Faculty of Health and Medical Sciences, Metropolitan University, Karachi, Pakistan
Zoha Zahra
Doctor, Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan
Ali Hamza Mirza
Postgraduate Researcher, University of Essex, United Kingdom.
Kiran Naved Khan
United Medical and Dental College, Karachi, Pakistan
Shama Nosherwani
Jhalawan Medical College, Khuzdar, Pakistan
Maaz Ubair Shaikh
Pharm D, University of Sindh, Jamshoro, Pakistan

Abstract

Background: Genetic susceptibility and sleep disturbances may be associated with neuronal injury before clinically apparent cognitive impairment. Objective: To examine whether objective sleep architecture modifies the association between Alzheimer’s disease polygenic risk and plasma neurofilament light chain (NFL) in midlife. Methods: This cross-sectional study analyzed 84 adults aged 40–60 years recruited through health screenings and workplace wellness programs in Islamabad–Rawalpindi, Pakistan. Participants had no reported cognitive complaints or diagnosed with cognitive impairment. Polygenic risk scores (PRS) were derived from genome-wide genotyping. Home polysomnography measured N3 sleep duration and wakefulness after sleep onset (WASO), and plasma NFL was measured using a single-molecule array assay. Pearson correlations and hierarchical linear regression examined associations and interactions, adjusting for age, sex, and body mass index. Results: PRS correlated positively with log-NFL (r = 0.31, p = 0.004) and inversely with N3 duration (r = −0.26, p = 0.017). The PRS × N3 interaction was negative (β = −0.31, p = 0.003), indicating a stronger PRS–NFL association at shorter N3 durations. The PRS × log-WASO interaction was not statistically significant (β = 0.14, p = 0.190). Conclusion: N3 duration modified the observed association between genetic susceptibility and plasma NFL. These cross-sectional findings do not establish causality or Alzheimer-specific pathology.

Article Details

Issue

Vol. 4 No. 1 (2026)

Section

Articles
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This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

[1]
Asma Riffaqat et al. 2026. The Association Between Polygenic Risk for Alzheimer’s, Objective Sleep Architecture, and Plasma Neurofilament Light Chain in Midlife. Journal of Health, Wellness and Community Research. 4, 1 (Jan. 2026), 1–8. DOI:https://doi.org/10.61919/wyfc0r72.

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