| Title: | Integrative prediction of Alzheimer's disease and related dementias using multi-omics aging clocks and genetic data |
| Journal: | Alzheimer's & Dementia |
| Published: | 28 Sep 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42805938/ |
| DOI: | https://doi.org/10.1002/alz.71869 |
Publication 21733
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Abstract
INTRODUCTION: We tested whether combining Alzheimer's disease and related dementias (ADRD) polygenic risk scores (PRS) with biological aging markers improves ADRD risk prediction.</p>
METHODS: In 16,215 UK Biobank (UKB) participants free of ADRD at baseline (median follow-up: 10.08 years), 397 incident diagnoses were identified. Biological aging measures included clinical, telomere, proteomic, and metabolomic aging markers. External validation/replication was performed in TwinGene (N = 3772; 331 cases).</p>
RESULTS: The fully integrated model achieved area under the curve (AUC) = 0.90 and area under the precision-recall curve (AUPRC) = 0.24 in the UKB held-out test set. PRS was the strongest predictor (subdistribution hazard ratio [sHR] = 2.24, 95% CI: 2.02-2.48), followed by ProtAge (sHR = 2.01, 95% CI: 1.13-3.58). The top predicted-risk quartile showed higher ADRD incidence (sHR = 16.73, 95% CI: 6.49-43.11). TwinGene showed moderate transportability (AUC = 0.757; AUPRC = 0.223) and preserved risk stratification (sHR = 4.02, 95% CI: 3.25-5.02).</p>
DISCUSSION: Integrating PRS and biological aging measures improved ADRD risk stratification.</p>
19 Keywords
- Aged
- Aging
- Alzheimer Disease
- Biological Clocks
- Dementia
- Female
- Follow-Up Studies
- Genetic Markers
- Genetic Predisposition to Disease
- Genetic Risk Score
- Humans
- Incidence
- Male
- Middle Aged
- Multiomics
- Predictive Learning Models
- Predictive Value of Tests
- UK Biobank
- United Kingdom
7 Authors
- Shayan Mostafaei
- Karolina Gustavsson
- Hampus Hagelin
- Jonathan K. L. Mak
- Trung Nghia Vu
- Ida K. Karlsson
- Sara Hägg
1 Application
| Application ID | Title |
|---|---|
| 22224 | Prospective studies of ageing and age-related diseases |
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