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Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation

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-symptoma...

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Autores principales: Chatterjee, Pratishtha, Tegg, Michelle, Pedrini, Steve, Fagan, Anne M., Xiong, Chengjie, Singh, Abhay K., Taddei, Kevin, Gardener, Samantha, Masters, Colin L., Schofield, Peter R., Multhaup, Gerhard, Benzinger, Tammie L. S., Morris, John C., Bateman, Randall J., Greenberg, Steven M., van Buchem, Mark A., Stoops, Erik, Vanderstichele, Hugo, Teunissen, Charlotte E., Hankey, Graeme J., Wermer, Marieke J. H., Sohrabi, Hamid R., Martins, Ralph N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000178/
https://www.ncbi.nlm.nih.gov/pubmed/33805778
http://dx.doi.org/10.3390/ijms22062931
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author Chatterjee, Pratishtha
Tegg, Michelle
Pedrini, Steve
Fagan, Anne M.
Xiong, Chengjie
Singh, Abhay K.
Taddei, Kevin
Gardener, Samantha
Masters, Colin L.
Schofield, Peter R.
Multhaup, Gerhard
Benzinger, Tammie L. S.
Morris, John C.
Bateman, Randall J.
Greenberg, Steven M.
van Buchem, Mark A.
Stoops, Erik
Vanderstichele, Hugo
Teunissen, Charlotte E.
Hankey, Graeme J.
Wermer, Marieke J. H.
Sohrabi, Hamid R.
Martins, Ralph N.
author_facet Chatterjee, Pratishtha
Tegg, Michelle
Pedrini, Steve
Fagan, Anne M.
Xiong, Chengjie
Singh, Abhay K.
Taddei, Kevin
Gardener, Samantha
Masters, Colin L.
Schofield, Peter R.
Multhaup, Gerhard
Benzinger, Tammie L. S.
Morris, John C.
Bateman, Randall J.
Greenberg, Steven M.
van Buchem, Mark A.
Stoops, Erik
Vanderstichele, Hugo
Teunissen, Charlotte E.
Hankey, Graeme J.
Wermer, Marieke J. H.
Sohrabi, Hamid R.
Martins, Ralph N.
author_sort Chatterjee, Pratishtha
collection PubMed
description 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.
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spelling pubmed-80001782021-03-28 Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation Chatterjee, Pratishtha Tegg, Michelle Pedrini, Steve Fagan, Anne M. Xiong, Chengjie Singh, Abhay K. Taddei, Kevin Gardener, Samantha Masters, Colin L. Schofield, Peter R. Multhaup, Gerhard Benzinger, Tammie L. S. Morris, John C. Bateman, Randall J. Greenberg, Steven M. van Buchem, Mark A. Stoops, Erik Vanderstichele, Hugo Teunissen, Charlotte E. Hankey, Graeme J. Wermer, Marieke J. H. Sohrabi, Hamid R. Martins, Ralph N. Int J Mol Sci Article 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. MDPI 2021-03-13 /pmc/articles/PMC8000178/ /pubmed/33805778 http://dx.doi.org/10.3390/ijms22062931 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chatterjee, Pratishtha
Tegg, Michelle
Pedrini, Steve
Fagan, Anne M.
Xiong, Chengjie
Singh, Abhay K.
Taddei, Kevin
Gardener, Samantha
Masters, Colin L.
Schofield, Peter R.
Multhaup, Gerhard
Benzinger, Tammie L. S.
Morris, John C.
Bateman, Randall J.
Greenberg, Steven M.
van Buchem, Mark A.
Stoops, Erik
Vanderstichele, Hugo
Teunissen, Charlotte E.
Hankey, Graeme J.
Wermer, Marieke J. H.
Sohrabi, Hamid R.
Martins, Ralph N.
Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation
title Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation
title_full Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation
title_fullStr Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation
title_full_unstemmed Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation
title_short Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation
title_sort plasma amyloid-beta levels in a pre-symptomatic dutch-type hereditary cerebral amyloid angiopathy pedigree: a cross-sectional and longitudinal investigation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000178/
https://www.ncbi.nlm.nih.gov/pubmed/33805778
http://dx.doi.org/10.3390/ijms22062931
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