Plasma levels of amyloid Aβ42/Aβ40 ratios are significantly decreased, whereas p-Tau181 and p-Tau217 proteins are significantly elevated in AD patients, representing major components of amyloid plaques and neurofibrillary tangles, the primary AD neuropathological cortical markers.  Recently, sensitive immunoassays capable of measuring the Aβ42/Aβ40 ratios, p-Tau181, and p-Tau217 in blood have been developed, with promising diagnostic potential for AD.  

AD plasma (n=63) and healthy control plasma (n=24) samples were analyzed with Fujirebio Lumipulse Aβ42/Aβ40 ratios, p-Tau181, and the Quanterix/Simoa AlZPath p-Tau217 immunoassays. Plasma Aβ42/Aβ40 ratios and p-Tau levels were evaluated within AD sample groups consisting of mild (n=15, MMSE >20-30), moderate (n=20, MMSE=15-20), and severe (n=28, MMSE<14) cognitive impairment, and healthy controls (n=24).

Analysis of the median Aβ42/Aβ40 ratios was lower in AD patients (p<0.0001), relative to controls. Conversely, the p-Tau181 and pTau217 assay revealed a significant increase in median p-Tau181 (6.7-fold) and p-Tau217 (6.28-fold) levels of the combined AD group (p<0.0001, n=63), relative to controls (n=24). All AD sample subgroups had distinguishable Aβ42/Aβ40 ratios (p=0.0021-<0.0001) and p-Tau181 and pTau217 levels (p<0.0012 to p<0.0001) relative to the control group. Aβ42/Aβ40 ratios, p-Tau181 and p-Tau217 levels were able to differentiate overall AD compared to controls (AUC=0.82, 0.93 and 0.92, respectively) and between the different AD clinical subgroups (Aβ42/Aβ40 ratios AUC=0.79-0.83; p-Tau181 AUC=0.82-0.93; and p-Tau217 AUC=0.80-0.92).

Lumipulse Aβ40/Aβ42 ratios, p-Tau181 and p-Tau217 assays demonstrated robust analytical performance and differentiated AD plasma from control plasma.  Plasma Aβ42/Aβ40 ratios, p-Tau181, and p-Tau217 biomarkers provide a practical diagnostic opportunity to identify AD patients.