Rational Use of Blood‐Based Biomarkers for Alzheimer's Disease: Navigating Between the Hope and the Hype

With better understanding of the pathologic processes of Alzheimer's disease, diagnostic methods have been developed to focus on specific biomarkers of disease detectable on brain imaging, cerebral spinal fluid, and, more recently, plasma. Although these tests do not establish a diagnosis of dementia, which requires a clinical evaluation, they can more precisely identify whether Alzheimer's disease is a contributing cause. The recent FDA approval of two blood-based biomarkers and the availability of others, including direct-to-consumer tests, has led to the potential for widespread use in primary and specialty care. However, the currently available blood-based biomarkers are more highly correlated with amyloid brain PET scans, which are less specific for symptomatic Alzheimer's disease, than with p-tau brain PET scans, which are strongly associated with changes in cognition. The value of a positive or negative blood-based biomarker depends on the test characteristics (e.g., sensitivity and specificity) of the specific test as well as the prevalence of the disease in the population. Clinicians ordering blood-based biomarkers must decide their value in the care of individual patients and be prepared to interpret the test results to their patients.