Screening for cerebral amyloid angiopathy based on serological biomarkers analysis using a dielectrophoretic force-driven biosensor platform

We aimed to analyze plasma amyloid-beta (A beta)(1-40) and A beta(1-42) using a highly sensitive dielectrophoretic-driven biosensor platform to demonstrate the possibility of precise cerebral amyloid angiopathy (CAA) diagnosis in participants classified according to A beta-positron emission tomography (PET) positivity and the neuroimaging criteria for CAA. We prospectively recruited 25 people with non-Alzheimer's disease (non-AD) and 19 patients with Alzheimer's disease (AD), which were further classified into the CAA- and CAA+ (possible and probable CAA) groups according to the modified Boston criteria. Patients underwent plasma A beta analysis using a highly sensitive nano-biosensor platform, A beta-PET scanning, and detailed neuropsychological testing. As a result, the average signal levels of A beta(1-42/1-40) differed significantly between the non-AD and AD groups, and the CAA+ group exhibited significantly higher A beta(1-40) signal levels than the CAA- group in both non-AD and AD groups. The concordance between the A beta(1-40) signal level and the neuroimaging criteria for CAA was nearly perfect, with areas under the curve of 0.954 (95% confidence interval (CI) 0.856-1.000), 0.969 (0.894-1.000), 0.867 (0.648-1.000), and 1.000 (1.000-1.000) in the non-AD/CAA- vs. non-AD/possible CAA, non-AD/CAA- vs. non-AD/probable CAA, AD/CAA- vs. AD/possible CAA, and AD/CAA- vs. AD/probable CAA groups, respectively. Higher A beta(1-40) signal levels were significantly associated with the presence of CAA according to regression analyses, and the neuroimaging pattern analysis partly supported this result. Our findings suggest that measuring plasma A beta(1-40) signal levels using a highly sensitive biosensor platform could be a useful non-invasive CAA diagnostic method.