A comparison of p-tau assays for the specificity to detect tau changes in Alzheimer's disease

INTRODUCTION: We evaluated differences in p-tau levels between Alzheimer's disease (AD), a condition with brain-specific changes in p-tau, and amyotrophic lateral sclerosis (ALS), a condition associated with increases in peripheral p-tau levels. METHODS: Cerebrospinal fluid and plasma from 668 participants were analyzed using immunoassays specific for the low-molecular-weight (LMW) tau isoforms present in the brain (i.e., p-tau217Lilly, p-tau181Lilly) and those that detect both LMW- and high-molecular-weight (HMW) tau expressed in the peripheral nervous system (i.e., p-tau217AlzPath, p-tau181UGOT). RESULTS: Increases in plasma p-tau in ALS versus controls were significantly smaller for the LMW-specific p-tau assays (15.9%–20.5%) compared with non-specific assays (92.0%–121.3%). The LMW-specific p-tau assays showed significantly larger plasma p-tau increases in AD versus ALS, discriminating AD from ALS with areas under the curve (AUCs; 0.890.93) higher than the AUCs of the non-specific assays (0.54–0.74). DISCUSSION: LMW-specific p-tau assays could be more useful in the diagnostic workup of AD, especially in population-based communities where conditions causing peripheral neuropathy are frequent. Highlights: Increases in plasma phosphorylated tau (p-tau) in amyotrophic lateral sclerosis (ALS) versus controls were significantly smaller for low-molecular-weight (LMW)–specific p-tau assays (i.e., p-tau217Lilly, p-tau181Lilly) compared with p-tau assays that also detect high-molecular-weight (HMW) assays (i.e., p-tau217AlzPath, p-tau181UGOT). The LMW-specific p-tau assays showed significantly larger increases in plasma p-tau in AD versus ALS compared with the non-specific assays. The LMW-specific p-tau assays discriminated AD from ALS with higher precision, showing significantly better performance than the non-specific assays. LMW-specific p-tau assays could be more useful in the diagnostic workup of AD, especially in population-based communities where conditions causing peripheral neuropathy (such as ALS) are frequent.