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Polygenic Hazard Score Predicts Synaptic and Axonal Degeneration and Cognitive Decline in Alzheimer's Disease Continuum Publisher Pubmed



Farhadieh ME1 ; Mozafar M2, 3 ; Sanaaee S4 ; Sodeifi P5 ; Kousha K6 ; Zare Y7 ; Zare S8 ; Maleki Rad N9 ; Jamshidigoharrizi F10, 11 ; Allahverdloo M12 ; Rahimi A13 ; Sadeghi M2, 3 ; Shafie M2, 3 ; Mayeli M14
Authors
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Authors Affiliations
  1. 1. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Sciences and Technology, University of Isfahan, Isfahan, Iran
  2. 2. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. NeuroTRACT Association, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Cellular and Molecular Biology, School of Advanced Sciences and Technology, Islamic Azad University of Medical Sciences, Tehran, Iran
  5. 5. School of Medicine, Azad University of Medical Sciences, Tehran, Iran
  6. 6. Department of Plant and Animal Biology, Faculty of Biological Sciences and Technology, University of Isfahan, Isfahan, Iran
  7. 7. Department of Psychology, Faculty of Literature, Humanities and Social Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
  8. 8. Department of Educational Psychology, Faculty of Psychology and Educational Science, Allameh Tabatabai University, Tehran, Iran
  9. 9. Department of Linguistic, Faculty of Literatures and Human Sciences, University of Ferdowsi, Mashhad, Iran
  10. 10. Department of Sociology-Cultural Sociology, Islamic Azad University, Kish International Branch, Hormozgan, Iran
  11. 11. Department of Psychology, Faculty of Psychology, Payame Noor University, Tehran, Iran
  12. 12. Department of Psychology, Faculty of Literature, Humanities and Social Sciences, Islamic Azad University, Zanjan, Iran
  13. 13. Institue of Translational Medicine, Budapest, Semmelwis, Hungary
  14. 14. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States

Source: Archives of Gerontology and Geriatrics Published:2024


Abstract

Background: Growth associated protein-43 (GAP-43) and neurofilaments light (NFL) are biomarkers of synaptic and axonal injury, and are associated with cognitive decline in Alzheimer's disease (AD) contiuum. We investigated whether Polygenic Hazard Score (PHS) is associated with specific biomarkers and cognitive measures, and if it can predict the relationship between GAP-43, NFL, and cognitive decline in AD. Method: We enrolled 646 subjects: 93 with AD, 350 with mild cognitive impairment (MCI), and 203 cognitively normal controls. Variables included GAP-43, plasma NFL, and PHS. A PHS of 0.21 or higher was considered high risk while a PHS below this threshold was considered low risk. A subsample of 190 patients with MCI with four years of follow-up cognitive assessments were selected for longitudinal analysis . We assessed the association of the PHS with AD biomarkers and cognitive measures, as well as the predictive power of PHS on cognitive decline and the conversion of MCI to AD. Results: PHS showed high diagnostic accuracy in distinguishing AD, MCI, and controls. At each follow-up point, high risk MCI patients showed higher level of cognitive impairment compared to the low risk group. GAP-43 correlated with all follow-up cognitive tests in high risk MCI patients which was not detected in low risk MCI patients. Moreover, high risk MCI patients progressed to dementia more rapidly compared to low risk patients. Conclusion: PHS can predict cognitive decline and impacts the relationship between neurodegenerative biomarkers and cognitive impairment in AD contiuum. Categorizing patients based on PHS can improve the prediction of cognitive outcomes and disease progression. © 2024
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