Interest in blood-based biomarkers for Alzheimer’s disease (AD) is growing, however current evidence and clinical consensus are clear, these assays are not appropriate for screening asymptomatic individuals, including for life insurance risk assessment.
Not Validated for Asymptomatic Populations
Based on current evidence, very few studies have evaluated biomarker performance in people without cognitive decline. Recently Jama Neurology featured commentary from AD clinicians who strongly cautioned that screening asymptomatic individuals would cause harm given the risks of misinterpretation and cause unnecessary anxiety in patients 1, 2. Complicating matters further, 20–30% of individuals with elevated levels of p-tau or amyloid beta will never develop symptoms 3. These tests can’t accurately predict whether people without cognitive impairment will ultimately develop AD.
Large Grey Zones and Biological Variability
Stand-alone biomarkers like p-tau217 have wide intermediate ranges that are difficult to interpret even in clinical settings. Combined ratios (e.g., p-tau with amyloid beta 42) reduce, but do not eliminate this uncertainty.
Interpretation is further complicated by natural biomarker elevations seen in certain ethnic groups and in individuals with chronic kidney disease, high BMI, diabetes, and other conditions. These population-level differences remain insufficiently understood and further studies are warranted.
Clinical Context Is Essential
Experts have stressed that AD biomarkers cannot be interpreted outside of clinical context, which is why current FDA-cleared AD assays specify this requirement. This limitation alone makes them incompatible with underwriting workflows where medical background is often incomplete.
Genetic and Proteotype Markers Not Deterministic
New ApoE proteotype assays approximate ApoE genotype, but—like genetic testing—results do not reliably predict who will or will not develop AD. Many ApoE4 homozygous individuals never become symptomatic, including some centenarians.
Future Directions: Multiprotein Panels
Emerging research on multiprotein and epigenetic signatures, particularly those focused on microglia and the glymphatic system, shows stronger predictive accuracy, particularly for disease progression and estimated age of onset. These tools are a few years away from potential clinical readiness.
Preanalytical Limitations
Lastly, it is worth noting that many of the current AD tests require rapid processing of the blood sample and cold-chain transport due to limited stability, adding operational barriers to adoption in the current life insurance preanalytical workflow.
Bottom Line
For now, blood-based AD biomarkers remain promising but not suitable for asymptomatic screening or life insurance risk assessment. CRL will continue to track this rapidly evolving field.
References:
1 doi: 10.1001/jamaneurol.2025.4726
2 doi: 10.1001/jama.2025.21573
3 Sponsored Neurology Blood-Based Biomarker Summit
About the Author
Dr. Fehling has been with CRL since 2008 and is a certified High Complexity Laboratory Director by the American Board of Bioanalysis (ABB). Dr. Fehling serves as the Laboratory Director for CRL’s Molecular Diagnostics/Esoteric Laboratory. More broadly, Dr. Fehling provides scientific leadership across all business units at CRL with her extensive experience in laboratory management, new assay development, and business development.