We have evaluated and validated Quanterix assays p-Tau217 (ALZpath), BD-Tau, p-Tau181, and Aβ42/Aβ40 ratio, and the Fujirebio p-Tau217 assay in plasma of AD subjects and healthy controls to characterize the discriminatory and correlative relationships for each assay and between clinical diagnosis groups.

Plasma levels of p-Tau217, BD-Tau, and p-Tau181 proteins are significantly higher in AD patients. Conversely, the amyloid Aβ42/Aβ40 ratio is considerably lower. These biomarkers are key components of amyloid plaques and neurofibrillary tangles in AD. Recently, sensitive immunoassays capable of measuring p-Tau217, BD-Tau, p-Tau181, and Aβ42/Aβ40 ratio in blood have been developed offering promising diagnostic potential for AD.  

AD (n=100) and healthy control (n=75) plasma samples were analyzed using Quanterix SIMOA p-Tau217 (ALZpath), BD-Tau, p-Tau181, and 4-Plex E (Aβ40, Aβ42, GFAP, NF-L) immunoassays performed on the HD-X analyzer, and the Fujirebio p-Tau217 immunoassay using the Lumipulse G1200 system. AD samples were selected based on a validated Fujirebio p-Tau217 cut-off >0.18 pg/mL, consistent with AD-amyloid pathology.

Analysis of p-Tau217 (ALZpath), BD-Tau, and p-Tau181 assays revealed a significant increase in the median levels in the AD group relative to age-matched controls. Conversely, the median Aβ42/Aβ40 ratio was significantly lower. AD samples had distinguishable p-Tau217 (p<0.0001, AUC=0.973), BD-Tau (p<0.0001, AUC=0.815), p-Tau181 (p<0.0001, AUC=0.878), Aβ42/Aβ40 ratio (p=0.0004, AUC=0.657), NF-L (p<0.0001, AUC=0.689), GFAP (p<0.0001, AUC=0.889) and Fujirebio p-Tau217 (p<0.0001, AUC=0.953) levels relative to the healthy control samples. Quanterix p-Tau217 (ALZpath)  and Fujirebio p-Tau217 measurements were strongly correlated (ρ=0.919),  p-Tau217 levels correlated with BD-Tau (ρ= 0.733), p-Tau181 (ρ=0.888), NF-L (ρ = 0.532), and GFAP (ρ =0.720). p-Tau217, BD-Tau, p-Tau181, and Aβ42/Aβ40 ratio levels could differentiate AD subjects from healthy controls. 

Blood plasma p-Tau217, BD-Tau, p-Tau181, and Aβ42/Aβ40 assays demonstrated robust analytical performance and differentiated AD subjects from healthy control subjects. These biomarkers provide a practical diagnostic opportunity to identify AD patients using blood samples.