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

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.

• Authors: 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 Hankey, Marieke J H Wermer, Hamid R Sohrabi, Ralph N Martins, The Dominantly Inherited Alzheimer Network
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 6 (Mar 13 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33805778 (Publication Type: Journal Article)

Chemical References

• APP protein, human
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Biomarkers
• Peptide Fragments
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)

Topics

• Adult
• Amyloid beta-Peptides (blood, genetics)
• Amyloid beta-Protein Precursor (blood, genetics)
• Asymptomatic Diseases
• Biomarkers (blood)
• Cerebral Amyloid Angiopathy, Familial (blood, diagnosis, genetics, pathology)
• Disease Progression
• Female
• Gene Expression
• Genes, Dominant
• Heterozygote
• Humans
• Longitudinal Studies
• Male
• Middle Aged
• Mutation
• Neuropsychological Tests
• Pedigree
• Peptide Fragments (blood, genetics)