Elevated Plasma Oligomeric Amyloid β-42 Is Associated with Cognitive Impairments in Cerebral Small Vessel Disease

Abstract

Due to the heterogeneity of amyloid β-42 (Aβ42) species, the potential correlation between plasma oligomeric Aβ42 (oAβ42) and cognitive impairments in cerebral small vessel disease (CSVD) remains unclear. Herein, a sandwich ELISA for the specific detection of Aβ42 oligomers (oAβ42) and total Aβ42 (tAβ42) 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 tAβ42 and oAβ42 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 Aβ42 tests further strengthened the predictive power of vascular risk factors for the presence of CSVD. Relative to tAβ42, oAβ42 showed a closer correlation with memory domains evaluated by neuropsychological tests. In conclusion, this sensitive ELISA protocol facilitated the detection of plasma Aβ42; Aβ42, especially its oligomeric form, can serve as a biosensor for the presence of CSVD and associated cognitive impairments represented by memory domains.

Keywords

• cerebral small vessel disease
• sandwich ELISA
• amyloid β-42
• oligomeric amyloid β-42
• white matter hyperintensities