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

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