Dataset Information

Sixteen-Year Longitudinal Evaluation of Blood-Based DNA Methylation Biomarkers for Early Prediction of Alzheimer's Disease.

ABSTRACT:

Background

DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown 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 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.

Results

EAA 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.

SUBMITTER: Schafer Hackenhaar F

PROVIDER: S-EPMC10473121 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Sixteen-Year Longitudinal Evaluation of Blood-Based DNA Methylation Biomarkers for Early Prediction of Alzheimer's Disease.

Schäfer Hackenhaar Fernanda F Josefsson Maria M Nordin Adolfsson Annelie A Landfors Mattias M Kauppi Karolina K Porter Tenielle T Milicic Lidija L Laws Simon M SM Hultdin Magnus M Adolfsson Rolf R Degerman Sofie S Pudas Sara S

Journal of Alzheimer's disease : JAD 20230101 4

<h4>Background</h4>DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown promise for Alzheimer's disease (AD) prediction.<h4>Objective</h4>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.<h4>Methods</h4>EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models ( ...[more]

PMID: 37393498

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Dataset Information

Sixteen-Year Longitudinal Evaluation of Blood-Based DNA Methylation Biomarkers for Early Prediction of Alzheimer's Disease.

Background

Objective

Methods

Results

Publications

Sixteen-Year Longitudinal Evaluation of Blood-Based DNA Methylation Biomarkers for Early Prediction of Alzheimer's Disease.

Similar Datasets

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