Decreased Cerebrospinal Fluid Amyloid ß 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy.

ABSTRACT

OBJECTIVE: Vascular amyloid ß (Aß) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker of CAA. We studied the diagnostic potential of the peptides Aß38, Aß40, Aß42, and Aß43 in patients with sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD). METHODS: Aß peptides were quantified by immunoassays in a discovery group (26 patients with sCAA and 40 controls), a validation group (40 patients with sCAA, 40 patients with AD, and 37 controls), and a group of 22 patients with D-CAA and 54 controls. To determine the diagnostic accuracy, the area under the curve (AUC) was calculated using a receiver operating characteristic curve with 95% confidence interval (CI). RESULTS: We found decreased levels of all Aß peptides in sCAA patients and D-CAA patients compared to controls. The difference was most prominent for Aß42 (AUC of sCAA vs controls for discovery 0.90, 95% CI = 0.82-0.99; for validation 0.94, 95% CI = 0.89-0.99) and Aß43 (AUC of sCAA vs controls for discovery 0.95, 95% CI = 0.88-1.00; for validation 0.91, 95% CI = 0.83-1.0). All Aß peptides except Aß43 were also decreased in sCAA compared to AD (CSF Aß38 AUC = 0.82, 95% CI = 0.71-0.93; CSF Aß40 AUC = 0.88, 95% CI = 0.80-0.96; CSF Aß42 AUC = 0.79, 95% CI = 0.66-0.92). INTERPRETATION: A combined biomarker panel of CSF Aß38, Aß40, Aß42, and Aß43 has potential to differentiate sCAA from AD and controls, and D-CAA from controls. ANN NEUROL 2023;931173-1186.