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The Polygenic Hazard Score Mediates the Association Between Plasma Neurofilament Light Chain and Brain Morphometry in Dementia Spectrum Publisher Pubmed



Nasiri H1 ; Azaraein MH2, 3 ; Shakeri S4 ; Sadeghi M5, 6 ; Sohrabiashlaghi A7 ; Berenjian S8 ; Karimian S9 ; Hoseinzadeh Z10 ; Rounkian MS11 ; Mayeli M12
Authors
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Authors Affiliations
  1. 1. Student Research Committee, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran
  2. 2. Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  3. 3. Iranian Scientific Society of Clinical Hypnosis, Tehran, Iran
  4. 4. Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  5. 5. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. School of Rehabilitation, Shiraz University of Medical Sciences, Shiraz, Iran
  7. 7. Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  8. 8. Department of Psychology, Islamic Azad University of Isfahan (Khorasgan) Branch, Isfahan, Iran
  9. 9. Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran
  10. 10. Department of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran
  11. 11. Student Research Committee, School of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
  12. 12. Department of Diagnostic Radiology and Biomedical Imaging, Yale School of Medicine, CT, United States

Source: Archives of Gerontology and Geriatrics Published:2025


Abstract

Introduction: Blood-based biomarkers such as plasma neurofilament light chain (pNfL) are crucial biomarkers for Alzheimer's disease (AD). Additionally, neuroimaging techniques such as tensor-based morphometry (TBM), which identify structural changes in the brain, can provide valuable insights into AD pathophysiology. However, the role of genetics in linking the blood based biomarkers and imaging findings has not been well understood. Therefore, we aimed to investigate whether the polygenic hazard score (PHS), affects the association between neurofibrillary tangles and neuritis plaques and brain imaging findings. Methods: Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we enrolled all participants for whom a complete dataset of pNfL, PHS, and TBM was available. Using Python, we analyzed the associations between pNfL levels and the TBM data of 567 participants incluidng 152 cognitively normal individuals, 309 participants with mild cognitive impairment (MCI), and 106 patients with AD. We used a mediation analysis to identify the effect of PHS in how pNfL is associated with TBM measures. Results: We found a negative correlation between the accelerated TBM measure and NfL levels in both the MCI and AD groups. The pNfL concentration predicted both accelerated statistical and anatomical TMB measures in patients with MCI. Furthermore, PHS mediatedthe association between statistical TBM measures and NfL levels in AD patients, to the extent that the significant association between NfL and TBM measures disappeared after accounting for PHS. Conclusion: We showed that although pNfL can predict the cognitiee decline and imaging findings in AD, this effect is mediated by the PHS. Therefore, PHS should be considered when investigating AD biomarkers and their corresponding imaging findings. © 2024 Elsevier B.V.
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