Beyond organ age gaps: comparing plasma proteomic metrics of organ biology in relation to brain structure and neurodegenerative disease.

Adding organ-level plasma proteomic age gap metrics to UK Biobank models yields a modest but largest ROC-AUC gain for Alzheimer’s disease (delta ROC-AUC = 0.037).

• Why it matters: Organ aging signals may extend beyond the CNS, but it is unclear whether different plasma proteomic organ metrics capture the same or complementary biology for brain structure and neurodegenerative risk.
• What they did: Using plasma proteomics from 52,667 UK Biobank participants and brain MRI from 5,078, the study built supervised XGBoost age-gap metrics, unsupervised PC1 organ metrics, and phenotype-guided PLS metrics, then tested associations with age, organ phenotypes, brain morphometry, and incident ICD-10 diagnoses.
• The result: The metric classes were related but not interchangeable, showed distinct links to brain structure and physiology, and partially mediated genetic risk for Alzheimer’s disease and stroke with small effect sizes (1–8%), while incremental prediction was modest overall.

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