Are Blood Tests for Alzheimer Disease Ready for Prime Time?

Abstract

This is a transformative time for patients with Alzheimer disease. Alzheimer disease is increasingly viewed as a treatable condition and managed like other major chronic diseases, such as heart disease and cancer. Management of Alzheimer disease includes early diagnosis with molecular confirmation, disease-modifying treatments that are initiated early in the disease course, better risk reduction and prevention strategies, and improved coordination of care.The transformation in Alzheimer disease care has been fueled by major advances in the detection of the key pathological hallmarks (the amyloid and tau proteins) for Alzheimer disease that began with tests of cerebrospinal fluid in the 1990s, positron emission tomographic (PET) scans for the amyloid protein in the early 2000s, and PET scans for the tau protein in 2010. However, PET scans are expensive and are not widely available. Plasma biomarkers, which seemed out of reach for many years because of the very low levels of amyloid and tau in blood samples, have more recently become reliable markers of Alzheimer disease pathology.Mass spectroscopy tests and ultrasensitive immunoassays of phosphorylated tau 217 (p-tau217) correlate well with cerebrospinal fluid and PET measures of cerebral amyloidosis and tau aggregation, and are specific to Alzheimer disease. [1][2][3] Treatment with monoclonal antibodies that lower amyloid plaque have recently been approved for the treatment of patients with early-stage Alzheimer disease, but the use of these therapeutic agents requires amyloid confirmation. Diagnosing Alzheimer disease accurately is challenging, especially in primary care. Having a reliable blood test is essential to help primary care physicians make an early and accurate diagnosis.In this issue of JAMA, Palmqvist et al 4 report whether a mass spectrometry blood test of the ratio of plasma p-tau217 relative to non-p-tau217 (percentage of p-tau217) combined with the amyloid-β 42 and amyloid-β 40 ratio (the amyloid probability score 2 [APS2]) correlate with Alzheimer disease pathology (amyloid-β and tau proteins) in patients being evaluated for mild dementia, mild cognitive impairment, and subjective cognitive decline in separate primary care and specialty care cohorts in Sweden. The accuracy of predicting the presence of Alzheimer disease pathology based on clinical evaluation alone was 61% in primary care and 73% in specialty care compared with 91% for the APS2 (the blood test) in both settings. The performance of the APS2 in these realworld clinical cohorts was largely driven by the percentage of p-tau217 measure.