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Acta Neuropathologica Communications
Published in: Acta Neuropathologica Communications 1/2024

Open Access 01-12-2024 | Biomarkers | Research

Cerebrospinal fluid shotgun proteomics identifies distinct proteomic patterns in cerebral amyloid angiopathy rodent models and human patients

Authors: Marc Vervuurt, Joseph M. Schrader, Anna M. de Kort, Iris Kersten, Hans J. C. T. Wessels, Catharina J. M. Klijn, Floris H. B. M. Schreuder, H. Bea Kuiperij, Jolein Gloerich, William E. Van Nostrand, Marcel M. Verbeek

Published in: Acta Neuropathologica Communications | Issue 1/2024

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Abstract

Cerebral amyloid angiopathy (CAA) is a form of small vessel disease characterised by the progressive deposition of amyloid β protein in the cerebral vasculature, inducing symptoms including cognitive impairment and cerebral haemorrhages. Due to their accessibility and homogeneous disease phenotypes, animal models are advantageous platforms to study diseases like CAA. Untargeted proteomics studies of CAA rat models (e.g. rTg-DI) and CAA patients provide opportunities for the identification of novel biomarkers of CAA. We performed untargeted, data-independent acquisition proteomic shotgun analyses on the cerebrospinal fluid of rTg-DI rats and wild-type (WT) littermates. Rodents were analysed at 3 months (n = 6/10), 6 months (n = 8/8), and 12 months (n = 10/10) for rTg-DI and WT respectively. For humans, proteomic analyses were performed on CSF of sporadic CAA patients (sCAA) and control participants (n = 39/28). We show recurring patterns of differentially expressed (mostly increased) proteins in the rTg-DI rats compared to wild type rats, especially of proteases of the cathepsin protein family (CTSB, CTSD, CTSS), and their main inhibitor (CST3). In sCAA patients, decreased levels of synaptic proteins (e.g. including VGF, NPTX1, NRXN2) and several members of the granin family (SCG1, SCG2, SCG3, SCG5) compared to controls were discovered. Additionally, several serine protease inhibitors of the SERPIN protein family (including SERPINA3, SERPINC1 and SERPING1) were differentially expressed compared to controls. Fifteen proteins were significantly altered in both rTg-DI rats and sCAA patients, including (amongst others) SCG5 and SERPING1. These results identify specific groups of proteins likely involved in, or affected by, pathophysiological processes involved in CAA pathology such as protease and synapse function of rTg-DI rat models and sCAA patients, and may serve as candidate biomarkers for sCAA.
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Metadata
Title
Cerebrospinal fluid shotgun proteomics identifies distinct proteomic patterns in cerebral amyloid angiopathy rodent models and human patients
Authors
Marc Vervuurt
Joseph M. Schrader
Anna M. de Kort
Iris Kersten
Hans J. C. T. Wessels
Catharina J. M. Klijn
Floris H. B. M. Schreuder
H. Bea Kuiperij
Jolein Gloerich
William E. Van Nostrand
Marcel M. Verbeek
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2024
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-023-01698-4

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