Cited by 47Multiple Sclerosis Research StudiesAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis

Augutis, Kristin, Axelsson, Markus, Portelius, Erik, Brinkmalm, Gunnar, Andreasson, Ulf, Gustavsson, Mikael K, Malmeström, Clas, Lycke, Jan +3 more·2013·Multiple Sclerosis Journal

Abstract

Background: Amyloid precursor protein (APP) and amyloid β (Aβ) peptides are intensely studied in neuroscience and their cerebrospinal fluid (CSF) measurements may be used to track the metabolic pathways of APP in vivo. Reduced CSF levels of Aβ and soluble APP (sAPP) fragments are reported in inflammatory diseases, including multiple sclerosis (MS); but in MS, the precise pathway of APP metabolism and whether it can be affected by disease-modifying treatments remains unclear. Objective: To characterize the CSF biomarkers of APP degradation in MS, including the effects of disease-modifying therapy. Methods: CSF samples from 87 MS patients (54 relapsing–remitting (RR) MS; 33 secondary progressive (SP) MS and 28 controls were analyzed for sAPP and Aβ peptides by immunoassays, plus a subset of samples was analyzed by immunoprecipitation and mass spectrometry (IP-MS). Patients treated with natalizumab or mitoxantrone were examined at baseline, and after 1–2 years of treatment. Results: CSF sAPP and Aβ peptide levels were reduced in MS patients; but they increased again towards normal, after natalizumab treatment. A multivariate model of IP-MS-measured Aβ species separated the SPMS patients from controls, with RRMS patients having intermediate levels. Conclusions: We confirmed and extended our previous observations of altered CSF sAPP and Aβ peptide levels in MS patients. We found that natalizumab therapy may be able to counteract the altered APP metabolism in MS. The CSF Aβ isoform distribution was found to be distinct in SPMS patients, as compared to the controls.

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Crossref · 10.1177/1352458512460603

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Authors
Augutis, K., Axelsson, M., Portelius, E., Brinkmalm, G., Andreasson, U., Gustavsson, M. K., Malmeström, C., Lycke, J., Blennow, K., Zetterberg, H., & Mattsson, N.
Affiliations
  • University of Gothenburg (SE)
  • Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Venue
Multiple Sclerosis Journal
Published
2012-10-15
Volume
19
Issue
5
Pages
543-552
ISSN
  • 1352-4585 (ISSN-L)
  • 1477-0970
OpenAlex
W2027107335
Cited by
47
References
32
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 1
FWCI
2.54
Type
journal article
Language
en
Open access
closed
Locations
  • Multiple Sclerosis Journal (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Biogen
  • IC Design Education Center
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
multiple sclerosis, cerebrospinal fluid biomarkers, amyloid-beta, amyloid precursor protein, APP metabolism, natalizumab, mitoxantrone, disease-modifying therapy, relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, amyloid-beta isoforms
MeSH terms
Natalizumab, Adult, Central Nervous System Agents, Chromatography, Liquid, Female, Humans, Immunoassay, Male, Middle Aged, Mitoxantrone, Multiple Sclerosis, Peptide Fragments, Mass Spectrometry, Biomarkers, Case-Control Studies, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Relapsing-Remitting, Immunoprecipitation, Tandem Mass Spectrometry, Antibodies, Monoclonal, Humanized

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