A possible blood plasma biomarker for early-stage Alzheimer's disease

Abstract

We sought to identify a usable biomarker from blood samples to characterize early-stage Alzheimer's disease (AD) patients, in order to facilitate rapid diagnosis, early therapeutic intervention, and monitoring of clinical trials. We compared metabolites from blood plasma in early-stage Alzheimer's disease patients with blood plasma from healthy controls using two different analytical platforms: Amino Acid Analyzer and Tandem Mass-Spectrometer. Early-stage Alzheimer's patient blood samples were obtained during an FDA-approved Phase IIa clinical trial (Clinicaltrial.gov NCT03062449). Participants included 25 early-stage Alzheimer's patients and 25 healthy controls in the United States. We measured concentrations of 2-aminoethyl dihydrogen phosphate and taurine in blood plasma samples. We found that plasma concentrations of a phospholipid metabolite, 2-aminoethyl dihydrogen phosphate, normalized by taurine concentrations, distinguish blood samples of patients with early-stage AD. This possible new Alzheimer's biomarker may supplement clinical diagnosis for early detection of the disease.

Fig 1. Representative chromatogram from the hitachi Amino Acid Analyzer method.

A. Taurine elutes at 1.6 min. 2-aminoethyl dihydrogen phosphate elutes at 2.1 min. Dark line is a representative Alzheimer’s patient sample. Grey line shows the absence of 2-aminoethyl dihydrogen phosphate in a control sample which is considered not detectable. Quantification was achieved by measuring the area under the curve in relation to known standard reference concentrations. B. Representative chromatogram from the tandem mass spectrometer method with 2-aminoethyl dihydrogen phosphate eluting at 2.05 min. The dotted line is an Alzheimer’s patient sample with an injection volume of 6 μl. The overlaid solid line represents the same sample spiked with a 2-aminoethyl dihydrogen phosphate standard. The identity of the peak at 2.1 min is unknown, however, this peak does not change as a result of the addition of 2-aminoethyl dihydrogen phosphate standard which confirms the identity of the peak at 2.05 min.

Fig 2. Scatter plot of patient age versus arcsin ratio of 2-aminoethyl dihydrogen phosphate / taurine).

Squares are healthy controls (n = 25) and circles are Alzheimer’s patients (n = 25). The arcsin ratio does not correlate with age, however, the incidence of Alzheimer’s disease does increase with patient age.