Synergistic Association between Plasma Aβ1-42 and p-tau in Alzheimer's Disease but Not in Parkinson's Disease or Frontotemporal Dementia.

Abstract

Beta-amyloid (Aβ1–42) triggers the phosphorylation of tau protein in Alzheimer’s disease (AD), but the relationship between phosphorylated tau (p-tau) and Aβ1–42 in the blood is not elucidated. We investigated the association in individuals with AD (n = 62, including amnesic mild cognitive impairment and dementia), Parkinson’s disease (n = 30), frontotemporal dementia (n = 25), and cognitively unimpaired controls (n = 41) using immunomagnetic reduction assays to measure plasma Aβ1–42 and p-tau181 concentrations. Correlation and regression analyses were performed to examine the relation between plasma levels, demographic factors, and clinical severity. Both plasma Aβ1–42 and p-tau concentrations were significantly higher in AD and frontotemporal dementia than in the controls and Parkinson’s disease. A significant positive association was found between plasma p-tau and Aβ1–42 in controls (r = 0.579, P < 0.001) and AD (r = 0.699, P < 0.001) but not in frontotemporal dementia or Parkinson’s disease. Plasma p-tau was significantly associated with clinical severity in the AD in terms of scores of clinical dementia rating (r = 0.288, P = 0.025) and mini-mental state examination (r = −0.253, P = 0.049). Regression analysis showed that plasma Aβ1–42 levels explain approximately 47.7% of the plasma p-tau levels in the AD after controlling age, gender, and clinical severity. While in non-AD participants, the clinical dementia rating explained about 47.5% of the plasma p-tau levels. The disease-specific association between plasma Aβ1–42 and p-tau levels in AD implies a possible synergic effect in mechanisms involving these two pathological proteins’ genesis.