Association between increased levels of amyloid-beta oligomers in plasma and episodic memory loss in Alzheimer's disease

Abstract

Objective The objectives of this study were to investigate whether the plasma levels of oligomeric amyloid-beta (OA beta) were affected in Alzheimer's disease (AD) and to examine the associations (or possible correlations) between plasma OA beta levels and memory performance. Method Thirty subjects with AD and 28 cognitively normal controls were recruited in the study. The multimer detection system (MDS) was used to measure the levels of OA beta in the plasma. In addition to assessing the general cognitive function with the Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Alzheimer's Disease Assessment Scale-cognitive portion (ADAS-Cog), the common objects memory test (COMT) was used to examine the episodic memory performance. Pearson's and partial correlation analyses were conducted to explore the associations between cognitive performance and OA beta levels in the plasma. A receiving operating curve (ROC) analysis was used to discriminate between the AD and control groups. Results The plasma OA beta levels in the AD group were significantly higher than those in the control group [1.88 (0.38) ng/ml vs 1.20 (0.40) ng/ml, p < 0.001]. The elevated levels of plasma OA beta showed a strong correlation with cognitive performance in patients with AD, including an inverse correlation with scores on the MMSE (r = - 0.43, p = 0.02), CASI (r = - 0.56, p < 0.01), and the immediate recall (r = - 0.45, p = 0.01), 5-min delayed recall (r = - 0.56, p < 0.01), and 30-min delayed recall (r = - 0.71, p < 0.001) tests of the COMT, and a positive correlation with the ADAS-Cog scores (r = 0.59, p < 0.001). The EDTA plasma A beta oligomer optical density (OD) value measured using the MDS could discriminate between the AD and control groups with an area under the curve (AUC) of 0.89. The optimal sensitivity and specificity were 82.1% and 90.0%, respectively. Conclusion The elevated levels of OA beta in the plasma distinguished the AD and control groups and were associated with the severity of symptoms, especially memory performance, in patients with AD. Our results suggested that plasma OA beta could potentially be a simple and non-invasive blood-based biomarker for AD diagnosis. Furthermore, longitudinal studies are warranted to explore the application of plasma OA beta levels as a valid diagnostic biomarker in patients with AD.