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

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were analyzed, including twenty-five studies published in papers, two studies presented at conferences and three unpublished studies.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.