Reliable Measurements of the β-Amyloid Pool in Blood Could Help in the Early Diagnosis of AD

Abstract

The present study was aimed at assessing the capability of Aβ1-40 and Aβ1-42 levels in undiluted plasma (UP), diluted plasma (DP), and cell bound (CB) to distinguish between early stages of Alzheimer's disease (AD), amnesic mild cognitive impairment (MCI), and healthy control (HC). Four blood samples from each participant were collected during one month and the levels of Aβ1-40 and Aβ1-42 were determined by a blinded proprietary ELISA sandwich (Araclon Biotech. Zaragoza, Spain). First striking result was that the amount of Aβ1-40 and Aβ1-42 in UP represented only a small proportion (~15%) of the total beta-amyloid pool in blood (βAPB) described here as the sum of Aβ1-40 and Aβ1-42 in blood where they are free in plasma, bound to plasma proteins, and bound to blood cells. Furthermore, we found that levels of Aβ1-40 and Aβ1-42 in UP, DP, and CB were significantly higher in MCI when compared to HC. On average, the total βAPB was 1.8 times higher in MCI than in HC (P = 0.03) and allowed to discriminate between MCI and HC with a sensitivity and specificity over 80%. Thus, quantification of several markers of the βAPB could be useful and reliable in the discrimination between MCI and HC.

Figure 1

((a)–(c)). Bar graphs of (a) Aβ1–40, (b) Aβ1-42 direct markers and (c) T40, T42, and total βAPB (T-AβPB) calculated markers. H, M, and A represent significance (P < 0.05) with regard to HC, MCI, and AD, respectively. *means P < 0.01.

Figure 2

((a)–(f)). Dot-plot for (a) DP Aβ1-40, (b) CB Aβ1-40, (c) UP Aβ1-42, (d) DP Aβ1-42, (e) T40 and (f) T-βAPB values in HC, MCI and AD participants. Numbers beside *indicate the value of outliers in the MCI and AD groups, which, for clarity of representation, are not represented at the same scale of the ordinate axis. The horizontal line with the number in parentheses represents the cut-off value between MCI and HC.