ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2026
Substituting blood-based biomarkers for imaging measures in Alzheimer's disease studies: implications for sample size and bias.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Probing effect modification by socioeconomic status in associations between blood biomarkers of neuropathology and cognitive outcomes in the United States and India.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Biomarker Variability Limits Individualized Amyloid Time Estimation in Alzheimer Disease.bioRxiv : the preprint server for biology · 2026Article
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Abstract
backgroundBlood-based biomarkers for Alzheimer's disease (AD) pathology are appealing options in large population-based studies due to their low cost, minimal invasiveness, and feasibility of collection in non-clinical settings. Despite these benefits, blood-based biomarkers have lower test-retest reliability than neuroimaging measures like amyloid positron emission tomography (amyloid-PET) Centiloids; trade-offs in power and bias remain unexplored.
methodsWe use data from Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) studies, which include both amyloid-PET and blood-based measures, to assess differences in statistical power, required sample size, and bias when replacing a neuroimaging measure with a blood-based measure. We use simulations parameterized based on these studies to show potential implications of using plasma p-tau 181 or p-tau 217, blood-based AD biomarkers, in place of Centiloids from amyloid-PET, when the biomarker is either the exposure or the outcome in an analysis of interest.
resultsWe demonstrated that substituting amyloid-PET Centiloids with a blood-based measure of p-tau can substantially reduce power, requiring 1.5-6.5 times the sample size to achieve 80% power compared to amyloid-PET. In addition, using a blood-based biomarker as the exposure can introduce significant regression dilution bias, attenuating estimated associations.
conclusionsWhile blood-based biomarkers are lower cost and easier to collect than neuroimaging measures, their use as proxies for AD pathology may introduce substantial methodological challenges, depending on the p-tau isoform. Consideration of the sample sizes they necessitate and their potential for bias is critical for the design and interpretation of studies employing these biomarkers.
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