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Sixteen-year longit...
Sixteen-year longitudinal evaluation of blood-based DNA methylation biomarkers for early prediction of Alzheimer’s disease
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- Schäfer Hackenhaar, Fernanda (author)
- Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Umeå centrum för funktionell hjärnavbildning (UFBI)
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- Josefsson, Maria, 1979- (author)
- Umeå universitet,Enheten för demografi och åldrandeforskning (CEDAR),Umeå centrum för funktionell hjärnavbildning (UFBI),Statistik
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- Nordin Adolfsson, Annelie (author)
- Umeå universitet,Psykiatri
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- Landfors, Mattias, 1977- (author)
- Umeå universitet,Patologi
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- Kauppi, Karolina (author)
- Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)
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- Porter, Tenielle (author)
- Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia; Curtin Medical School, Curtin University, Bentley, WA, Australia
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- Milicic, Lidija (author)
- Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
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- Laws, Simon M. (author)
- Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia; Curtin Medical School, Curtin University, Bentley, WA, Australia
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- Hultdin, Magnus (author)
- Umeå universitet,Patologi
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- Adolfsson, Rolf (author)
- Umeå universitet,Psykiatri
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- Degerman, Sofie, 1977- (author)
- Umeå universitet,Patologi,Institutionen för klinisk mikrobiologi
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- Pudas, Sara, Docent, 1983- (author)
- Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Umeå centrum för funktionell hjärnavbildning (UFBI)
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(creator_code:org_t)
- IOS Press, 2023
- 2023
- English.
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In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 94:4, s. 1443-1464
- Related links:
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https://doi.org/10.3...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Subject headings
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- Background: DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, hasshown promise for Alzheimer’s disease (AD) prediction.Objective: Testing long-term predictive ability (>15 years) of existing DNAm-based epigenetic age acceleration (EAA)measures and identifying novel early blood-based DNAm AD-prediction biomarkers.Methods: EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models(LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16years before clinical onset, and post-onset follow-up. NovelDNAmbiomarkers were generated with epigenome-wide LMMs,and Sparse Partial Least Squares Discriminant Analysis applied at pre- (10–16 years), and post-AD-onset time-points.Results: EAA did not differentiate cases from controls during the follow-up time (p > 0.05). Three new DNA biomarkersshowed in-sample predictive ability on average 8 years pre-onset, after adjustment for age, sex, and white blood cell proportions(p-values: 0.022-<0.00001). Our longitudinally-derived panel replicated nominally (p = 0.012) in an external cohort (n = 146cases, 324 controls). However, its effect size and discriminatory accuracy were limited compared to APOE 4-carriership(OR = 1.38 per 1 SD DNAmscore increase versus OR= 13.58 for 4-allele carriage; AUCs = 77.2% versus 87.0%). Literaturereview showed low overlap (n = 4) across 3275 AD-associated CpGs from 8 published studies, and no overlap with ouridentified CpGs.Conclusion: The limited predictive value of EAA for AD extends prior findings by considering a longer follow-up time, andwith appropriate control for age, sex, APOE, and blood-cell proportions. Results also highlight challenges with replicatingdiscriminatory or predictive CpGs across studies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Keyword
- Alzheimer’s disease
- biomarkers
- DNA methylation
- epigenomics
- longitudinal studies
Publication and Content Type
- ref (subject category)
- art (subject category)
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Schäfer Hackenha ...
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Josefsson, Maria ...
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Nordin Adolfsson ...
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Landfors, Mattia ...
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Kauppi, Karolina
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Porter, Tenielle
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Milicic, Lidija
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Laws, Simon M.
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Hultdin, Magnus
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Adolfsson, Rolf
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Degerman, Sofie, ...
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Pudas, Sara, Doc ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Other Basic Medi ...
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Journal of Alzhe ...
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Umeå University