ArticleJournal of Alzheimer's disease : JAD2023
Sixteen-Year Longitudinal Evaluation of Blood-Based DNA Methylation Biomarkers for Early Prediction of Alzheimer's Disease.
Article in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Longitudinal Sparse Single-Omics Factor Analysis for High-Dimensional Blood Biomarkers in Alzheimer's Disease.Statistics in medicine · 2026Article
- Blood DNA methylation signature for incident dementia: Evidence from longitudinal cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- AD-GCN: A novel graph convolutional network integrating multi-omics data for enhanced Alzheimer's disease diagnosis.PloS one · 2025Article
- Blood-based multivariate methylation risk score for cognitive impairment and dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown promise for Alzheimer's disease (AD) prediction.
objectiveTesting 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.
methodsEAA 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 16 years before clinical onset, and post-onset follow-up. Novel DNAm biomarkers 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.
resultsEAA did not differentiate cases from controls during the follow-up time (p > 0.05). Three new DNA biomarkers showed 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 = 146 cases, 324 controls). However, its effect size and discriminatory accuracy were limited compared to APOEɛ4-carriership (OR = 1.38 per 1 SD DNAm score increase versus OR = 13.58 for ɛ4-allele carriage; AUCs = 77.2% versus 87.0%). Literature review showed low overlap (n = 4) across 3275 AD-associated CpGs from 8 published studies, and no overlap with our identified CpGs.
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