Blood-Based Biomarkers for Alzheimer Disease in Primary Care: The Gap Between Biology and Clinical Utility.

Blood-based biomarkers (BBMs) for Alzheimer disease (AD) have accelerated the prospect of earlier and more accessible detection of AD pathology, potentially beyond specialist settings. However, their introduction in primary care raises important questions about clinical sequencing, interpretability, pathway consequences, and real-world utility. In this Personal View, we argue that the main barrier to responsible implementation is not analytical performance alone, but the absence of a sufficiently defined diagnostic infrastructure in which a test result has a clear and actionable role. In low-prevalence and clinically heterogeneous primary care populations, inadequate clinical anchoring and unstable pretest probability may undermine interpretability and promote category drift from diagnostic testing towards case-finding or quasiscreening. Moreover, the value of a rule-out strategy depends on whether a negative result meaningfully changes management. Until stronger evidence, clearer guidance, and appropriate service conditions are in place, primary care use of AD BBMs should remain selective, clinically anchored, and pathway-dependent.