Changes in plasma biomarkers differentiate clinical stages of Alzheimer's disease using immunomagnetic reduction assays

Abstract

Background Many groups have been using immunomagnetic reduction (IMR) for assaying plasma amyloid-β 1-40 (Aβ1-40) peptide, Aβ1-42 peptide and total tau protein (T-Tau) in cognitively normal controls (NC), patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD). Tremendous results have been independently reported. Objective We used traditional knowledge databases (e.g., PubMed, Embase), papers published at international conferences, and private communications to obtain data involving the use of IMR assay for plasma biomarkers of plasma Aβ1-40, Aβ1-42, and T-Tau in NC, aMCI, and ADD. Methods Results of thirty studies were analyzed, including twenty-five studies published in papers, two studies presented at conferences and three unpublished studies. Results Among the thirty studies, there were 1189 subjects of NC, 544 aMCI patients and 853 ADD patients. The average value of plasma Aβ1-40 in subjects significantly decreased from NC (59.72 pg/ml) to aMCI (45.92 pg/ml, p < 0.0001), which was no significant different from ADD (48.34 pg/ml, p > 0.05). The average level of plasma Aβ1-42 significantly increased from NC (15.72 pg/ml) to aMCI (17.66 pg/ml, p < 0.0001), which was not significantly different from ADD (19.39 pg/ml, p > 0.05). However, the average level of plasma T-Tau significantly increased from NC (17.92 pg/ml) to aMCI (28.26 pg/ml, p < 0.0001), further significantly increased to AD (35.51 pg/ml, p < 0.001). Conclusions Plasma Aβ1-40, Aβ1-42, and T-Tau levels are able to discriminate NC from patients with aMCI and ADD. Plasma T-Tau levels are disease-severity dependent.