CSF amyloid-beta 1-38 and 1-42 in FTD and AD: Biomarker performance critically depends on the detergent accessible fraction

Abstract

Cerebrospinal fluid (CSF) A beta I-38, A beta 1-40, and A beta 1-42 were comparatively analyzed by amyloid-beta SDS-PAGE with Western immunoblot (A beta-SDS-PAGE/immunoblot), electrochemiluminescence detection and ELISA (MSD/ELISA) in patients with Alzheimer's disease (AD, n = 40), frontotemporal dementia (FTD, n = 30), and other dementias (n = 50) and nondemented disease controls (n = 30). CSF A beta-peptide concentrations were higher and selective decreases of CSF A beta 1-38 in FTD and A beta 1-42 in AD were more evident as measured after SDS-denaturizing of samples by A beta-SDS-PAGE/immunoblot. The SDS-accessible pool of CSF A beta 1-38 and A beta 1-42, represented by the individual gain of A beta-peptide yield using A beta-SDS-PAGE/immunoblot, was reduced in both FTD and AD. Accordingly, biomarker accuracies of A beta 1-38 and A beta 1-42 for detection of FTD and AD, respectively declined as determined by MSD/ELISA. We conclude that a pool of CSF A beta 1-38 and A beta 1-42, which shows disease-specific reductions in FTD and AD, may be bound to carriers and can be released by SDS. Assessing this SDS-accessible A beta-peptide pool may crucially enhance the accuracy of CSF biomarker tests. Identifying disease-specific binding properties of affected A beta carriers may elucidate pathogenic aspects and open up a novel field for therapeutic approaches.