International Journal of Molecular Sciences | March 13, 2021

Chatterjee P, Tegg M, Pedrini S, Fagan AM, Xiong C, Singh AK, Taddei K, Gardener S, Masters CL, Schofield PR, Multhaup G, Benzinger TLS, Morris JC, Bateman RJ, Greenberg SM, van Buchem MA, Stoops E, Vanderstichele H, Teunissen CE, Hankey GJ, Wermer MJH, Sohrabi HR, Martins RN and Network tDIA

International journal of molecular sciences. 2021;22:2931

DOI: https://doi.org/10.3390/ijms22062931

This study was performed using a Simoa Homebrew assay.

Abstract

Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3–4 years later (NC = 8; MC = 9). Plasma Aβ1-40 and Aβ1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(Aβ1-40: p = 0.001; Aβ1-42: p = 0.0004) and T2 (Aβ1-40: p = 0.001; Aβ1-42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aβ1-40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma Aβ1-42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma Aβ may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger sample sets are required