Contextualizing Blood-Based Biomarkers for Dementia Globally.

Area of Science:

• Neurology
• Biomarkers
• Public Health

Background:

• Blood-based biomarkers (BBMs) are emerging for Alzheimer's disease (AD) diagnosis, offering less invasive and scalable biological characterization.
• Current evidence largely stems from high-income settings, raising concerns about generalizability and equitable implementation in diverse populations.

Purpose of the Study:

• To advocate for context-aware interpretation frameworks for BBMs in Alzheimer's disease.
• To emphasize the need to integrate social, environmental, and health system determinants into BBM interpretation.

Main Methods:

• Conceptual analysis using the amyloid, tau, and neurodegeneration (AT(N)) system as a framework.
• Examination of how social determinants, life-course exposures, and health system factors influence biomarker distributions.
• Review of evidence from underrepresented settings, such as Latin America, on factors modifying biomarker levels.

Main Results:

• BBMs should be used within defined contexts (triage, diagnosis, prognosis) rather than as universal diagnostic substitutes.
• Social determinants and health factors (e.g., cardiometabolic load) can significantly alter baseline biomarker levels.
• Uncritical transfer of cutoffs from high-income settings may lead to misinterpretation in diverse populations.

Conclusions:

• Responsible adoption of BBMs for AD requires aligning biological signals with clinical context, social/environmental conditions, and system capacity.
• Failure to align BBMs with context risks misclassification, inequitable care, biased trials, and distorted disease burden estimates.
• Context-aware interpretation is crucial for maximizing the potential of BBMs to expand access to AD biological characterization.