Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis
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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CSF+/PET− subjects are not all early Aβ accumulators since this state also can be caused by CSF analytical factors, failed PET scans, and medical conditions other than AD.
“Nonetheless, we acknowledge that CSF+/PET− subjects are not all early Aβ accumulators since this state also can be caused by CSF analytical factors, failed PET scans, and medical conditions other than AD36–38.”
From Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity (2017) · cites this paper as [36]
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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
- ORCID
- Venue
- Multiple Sclerosis Journal
- Publisher
- SAGE Publications
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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