Plasma amyloid-beta levels in a pre-symptomatic Dutch-type hereditary cerebral amyloid angiopathy pedigree: a cross-sectional and longitudinal investigation

Author(s):
Chatterjee, P.; Tegg, M.; Pedrini, S.; Fagan, A.M.; Xiong, C.J.; Singh, A.K.; Taddei, K.; Gardener, S.; Masters, C.L.; Schofield, P.R.; Multhaup, G.; Benzinger, T.L.S.; Morris, J.C.; Bateman, R.J.; Greenberg, S.M.; Buchem, M.A. van (0000-0003-1881-1998); Stoops, E.; Vanderstichele, H.; Teunissen, C.E.; Hankey, G.J.; Wermer, M.J.H.; Sohrabi, H.R.; Martins, R.N.; Dominantly Inherited Alzheimer Net
Published
2021
Publication type
Article / Letter to editor

Abstract

Plasma amyloid-beta (A beta) 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 A beta alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two A beta 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 A beta 1-40 and A beta 1-42 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(A beta 1-40: p = 0.001; A beta 1-42: p = 0.0004) and T2 (A beta 1-40: p = 0.001; A beta 1-42: 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 A beta 1-40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma A beta 1-42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma A beta 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.

amyloid-betaplasma amyloid-betablood biomarkerscerebral amyloid angiopathyearly diagnosishereditary cerebral haemorrhage with amyloidosis—Dutch typesingle molecule array platform
Date issued
2021-03-01
Language
English
Publisher
MDPI
Is part of
International Journal of Molecular Sciences (2021), No. 6
hdl
1887/3214717
doi
10.3390/ijms22062931
URL
https://www.mdpi.com/1422-0067/22/6/2931/pdf