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

Pratishtha Chatterjee, Michelle Tegg, Steve Pedrini, Anne M. Fagan, Chengjie Xiong, Abhay K. Singh, Kevin Taddei, Samantha Gardener, Colin L. Masters, Peter R. Schofield, Gerhard Multhaup, Tammie L. S. Benzinger, John C. Morris, Randall J. Bateman, Steven M. Greenberg, Mark A. van Buchem, Erik Stoops, Hugo Vanderstichele, Charlotte E. Teunissen, Graeme J. HankeyMarieke J. H. Wermer, Hamid R. Sohrabi, Ralph N. Martins*, The Dominantly Inherited Alzheimer Network

*Corresponding author for this work

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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 covari-ates, 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.

Original languageEnglish
Article number2931
Pages (from-to)1-12
Number of pages12
JournalInternational Journal of Molecular Sciences
Volume22
Issue number6
DOIs
Publication statusPublished - 2 Mar 2021

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Amyloid‐beta
  • Blood biomarkers
  • Cerebral amyloid angiopathy
  • Early diagnosis
  • Hereditary cerebral haemorrhage with amyloidosis—Dutch type
  • Plasma amyloid‐beta
  • Single molecule array platform

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