| Title: |
Profiling amyloid‐β peptides as diagnostic biomarkers for cerebral amyloid angiopathy |
| Authors: |
van den Berg, Emma; de Kort, Anna M.; Kersten, Iris; Brinkmalm, Gunnar; Johansson, Kjell; Marques, Tainá M.; Jäkel, Lieke; Gobom, Johan; Stoops, Erik; Portelius, Erik; Gkanatsiou, Eleni; Abdo, Wilson F.; Rasing, Ingeborg; Voigt, Sabine; Koemans, Emma A.; Kaushik, Kanishk; Warren, Andrew D.; Greenberg, Steven M.; Terwindt, Gisela M.; Wermer, Marieke J.H.; Klijn, Catharina J.M.; Schreuder, Floris H.B.M.; Zetterberg, Henrik; Blennow, Kaj; Kuiperij, H. Bea; Verbeek, Marcel M. |
| Source: |
Alzheimer's & Dementia ; volume 19, issue S15 ; ISSN 1552-5260 1552-5279 |
| Publisher Information: |
Wiley |
| Publication Year: |
2023 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background Amyloid‐β (Aβ) deposits are the main pathological hallmark of cerebral amyloid angiopathy (CAA) and Alzheimer’s disease (AD). Vascular deposits in CAA mainly consist of Aβ 40 , whereas Aβ 42 is the predominant peptide in parenchymal plaques in AD. The diagnostic accuracy of other Aβ species in CAA remains understudied. We aimed to investigate the biomarker potential of various Aβ peptides for the differentiation of sporadic (sCAA) and hereditary Dutch‐type CAA (D‐CAA) from AD and controls. Method Cerebrospinal fluid (CSF) Aβ 38 , Aβ 40 , Aβ 42 , and Aβ 43 levels were quantified by immunoassays in discovery (26 sCAA patients, 40 controls) and validation cohorts (40 sCAA patients, 40 AD patients, 37 controls), and D‐CAA patients (10 presymptomatic, 26 controls; 12 symptomatic, 28 controls). In a subset of samples (25 sCAA, 50 AD, 23 controls), we confirmed results using an extended panel of Aβ peptides (including Aβ 34 , Aβ 37 , and Aβ 39 , but not Aβ 43 ) quantified by liquid chromatography mass spectrometry (LC‐MS). Area‐under‐the‐curve (AUC) was calculated using receiver operating characteristic curve to assess diagnostic accuracies. Result We found decreased levels of all Aβ peptides (quantified by immunoassays) in sCAA and D‐CAA compared with controls (Figures 1 and 2). All Aβ peptides, except Aβ 43 , were also decreased in sCAA compared with AD (Figure 1). LC‐MS verified the lower CSF levels of six Aβ peptides in sCAA compared with controls (Figure 3). All peptides, except Aβ 42 , were also decreased in sCAA compared with AD. Single peptide levels (using either method) differentiated sCAA from AD (immunoassays AUC 0.68‐0.88; LC‐MS AUC 0.51‐0.75) and controls (immunoassays AUC 0.61‐0.95; LC‐MS AUC 0.69‐0.85). Combinations of all Aβ peptides differentiated sCAA from AD patients (immunoassays AUC 0.93; LC‐MS AUC 0.84) and controls (immunoassays AUC 0.89‐0.98; LC‐MS AUC 0.91) with high accuracy. Conclusion CAA and AD each show a distinct disease‐specific profile of CSF Aβ peptides. All ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/alz.076080 |
| Availability: |
https://doi.org/10.1002/alz.076080 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.BEC5A069 |
| Database: |
BASE |