Elevated Plasma Oligomeric Amyloid β-42 Is Associated with Cognitive Impairments in Cerebral Small Vessel Disease
2023
Wensheng Qu | Liding Zhang | Xiaohan Liang | Zhiyuan Yu | Hao Huang | Jing Zhao | Yinping Guo | Xirui Zhou | Shabei Xu | Haiming Luo | Xiang Luo
Due to the heterogeneity of amyloid β-42 (Aβ<sub>42</sub>) species, the potential correlation between plasma oligomeric Aβ<sub>42</sub> (oAβ<sub>42</sub>) and cognitive impairments in cerebral small vessel disease (CSVD) remains unclear. Herein, a sandwich ELISA for the specific detection of Aβ<sub>42</sub> oligomers (oAβ<sub>42</sub>) and total Aβ<sub>42</sub> (tAβ<sub>42</sub>) was developed based on sequence- and conformation-specific antibody pairs for the evaluation of plasma samples from a Chinese CSVD community cohort. After age and gender matching, 3-Tesla magnetic resonance imaging and multidimensional cognitive assessment were conducted in 134 CSVD patients and equal controls. The results showed that plasma tAβ<sub>42</sub> and oAβ<sub>42</sub> levels were significantly elevated in CSVD patients. By regression analysis, these elevations were correlated with the presence of CSVD and its imaging markers (i.e., white matter hyperintensities). Plasma Aβ<sub>42</sub> tests further strengthened the predictive power of vascular risk factors for the presence of CSVD. Relative to tAβ<sub>42</sub>, oAβ<sub>42</sub> showed a closer correlation with memory domains evaluated by neuropsychological tests. In conclusion, this sensitive ELISA protocol facilitated the detection of plasma Aβ<sub>42</sub>; Aβ<sub>42</sub>, especially its oligomeric form, can serve as a biosensor for the presence of CSVD and associated cognitive impairments represented by memory domains.
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