van den Berg, Emma;
Kersten, Iris;
Brinkmalm, Gunnar;
Johansson, Kjell;
de Kort, Anna M;
Klijn, Catharina JM;
Schreuder, Floris HBM;
... Verbeek, Marcel M; + view all
(2024)
Profiling amyloid-β peptides as biomarkers for cerebral amyloid angiopathy.
Journal of Neurochemistry
10.1111/jnc.16074.
(In press).
Preview |
PDF
Profiling amyloid peptides as biomarkers for cerebral amyloid angiopathy.pdf - Published Version Download (3MB) | Preview |
Abstract
Brain amyloid-β (Aβ) deposits are key pathological hallmarks of both cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Microvascular deposits in CAA mainly consist of the Aβ40 peptide, whereas Aβ42 is the predominant variant in parenchymal plaques in AD. The relevance in pathogenesis and diagnostic accuracy of various other Aβ isoforms in CAA remain understudied. We aimed to investigate the biomarker potential of various Aβ isoforms in cerebrospinal fluid (CSF) to differentiate CAA from AD pathology. We included 25 patients with probable CAA, 50 subjects with a CSF profile indicative of AD pathology (AD-like), and 23 age- and sex-matched controls. CSF levels of Aβ1-34 , Aβ1-37 , Aβ1-38 , Aβ1-39 , Aβ1-40 , and Aβ1-42 were quantified by liquid chromatography mass spectrometry. Lower CSF levels of all six Aβ peptides were observed in CAA patients compared with controls (p = 0.0005-0.03). Except for Aβ1-42 (p = 1.0), all peptides were decreased in CAA compared with AD-like subjects (p = 0.007-0.03). Besides Aβ1-42 , none of the Aβ peptides were decreased in AD-like subjects compared with controls. All Aβ peptides combined differentiated CAA from AD-like subjects better (area under the curve [AUC] 0.84) than individual peptide levels (AUC 0.51-0.75). Without Aβ1-42 in the model (since decreased Aβ1-42 served as AD-like selection criterion), the AUC was 0.78 for distinguishing CAA from AD-like subjects. CAA patients and AD-like subjects showed distinct disease-specific CSF Aβ profiles. Peptides shorter than Aβ1-42 were decreased in CAA patients, but not AD-like subjects, which could suggest different pathological mechanisms between vascular and parenchymal Aβ accumulation. This study supports the potential use of this panel of CSF Aβ peptides to indicate presence of CAA pathology with high accuracy.
| Type: | Article |
|---|---|
| Title: | Profiling amyloid-β peptides as biomarkers for cerebral amyloid angiopathy |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/jnc.16074 |
| Publisher version: | https://doi.org/10.1111/jnc.16074 |
| Language: | English |
| Additional information: | © 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Alzheimer's disease, amyloid-β, biomarkers, cerebral amyloid angiopathy, cerebrospinal fluid, mass spectrometry |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10187629 |
Archive Staff Only
 |
View Item |
