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

Abstract

Abstract 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‐tau217 Lilly , p‐tau181 Lilly ) and those that detect both LMW‐ and high‐molecular‐weight (HMW) tau expressed in the peripheral nervous system (i.e., p‐tau217 AlzPath , p‐tau181 UGOT ). 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.