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

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.