Integrative prediction of Alzheimer's disease and related dementias using multi-omics aging clocks and genetic data.

Authors

Shayan Mostafaei, Karolina Gustavsson, Hampus Hagelin, Jonathan K L Mak, Trung Nghia Vu, Ida K Karlsson, Sara Hägg

Published in

Alzheimer's & dementia : the journal of the Alzheimer's Association. Volume 22. Issue 10. Pages e71869.

Abstract

We tested whether combining Alzheimer's disease and related dementias (ADRD) polygenic risk scores (PRS) with biological aging markers improves ADRD risk prediction.
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).
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).
Integrating PRS and biological aging measures improved ADRD risk stratification.

PMID:
42805938
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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