Correlations and Diagnostic Performances of Plasma Amyloid β 1–42 Peptide, Phosphorylated Tau Protein (Threonine 181), and Total Tau Protein in Alzheimer’s Disease

Abstract Abnormal amyloid β peptide in neurons is associated with the phosphorylation of tau protein in the development of Alzheimer’s disease, resulting in abundant total tau protein release in the brain due to neuronal deterioration. These findings suggest potential correlations among the levels of the amyloid β peptide, phosphorylated tau, and total tau protein in patients with Alzheimer’s disease. In this study, an ultrasensitive immunoassay, the so-called immunomagnetic reduction (IMR), was used to measure the levels of amyloid β 1–42 peptide (Aβ1–42), phosphorylated tau protein at threonine 181 (pTau181), and total tau protein (T-Tau) in human blood to explore these potential correlations. Forty-three cognitively unimpaired (CU) subjects, thirty-five patients with amnestic mild cognitive impairment (aMCI), and 11 patients with early-stage Alzheimer’s disease dementia (eADD) were enrolled in this cross-sectional cohort. Moderate or strong correlations were detected among plasma Aβ1–42, pTau181, and T-Tau levels in the pooled clinical groups. Among the individual or combined biomarkers, plasma Aβ1–42xT-Tau demonstrated strong performance for predicting aMCI and eADD, with both clinical sensitivity and specificity exceeding 0.9 within this cohort. The superior performance of Aβ1–42xT-Tau could have occurred because measured Aβ1–42 consists of oligomers, and measured T-Tau protein is potentially derived from the brain as detected with IMR. These results are phenomenologically consistent with the idea that cellular Aβ1–42 modulates the phosphorylation of tau protein in Alzheimer’s disease.