Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis
Abstract
Background Cell and animal experiments have shown that β-site APP-cleaving enzyme 1 (BACE1) may be involved in myelination. Objective Here, we assess the association of cerebrospinal fluid (CSF) BACE1 activity with multiple sclerosis (MS). Methods BACE1 activity and levels of secreted amyloid precursor protein (APP) and amyloid-β (Aβ) isoforms were analyzed in CSF from 100 patients with MS and 114 neurologically healthy controls. Patients with systemic lupus erythematosus (SLE), 26 with and 41 without cerebral engagement, were also included to enable comparisons with regards to another autoimmune disease. A subset of patients with MS and controls underwent a second lumbar puncture after 10 years. Results MS patients had lower CSF BACE1 activity than controls ( P = 0.03) and patients with cerebral SLE ( P < 0.001). Patients with cerebral SLE had higher BACE1 activity than any other group ( P < 0.05 for all comparisons). BACE1 activity correlated with the different amyloid markers in all study groups. BACE1 activity decreased over 10 years in the MS group ( P = 0.039) and correlated weakly with clinical disease severity scores in an inverse manner. Conclusions These results suggest an involvement of BACE1 in the MS disease process.
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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 [37]
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Self-citation
- Authors
- Mattsson, N., Axelsson, M., Haghighi, S., Malmeström, C., Wu, G., Anckarsäter, R., Sankaranarayanan, S., Andreasson, U., Fredrikson, S., Gundersen, A., Johnsen, L., Fladby, T., Tarkowski, A., Trysberg, E., Wallin, A., Anckarsäter, H., Lycke, J., Andersen, O., Simon, A., Blennow, K., & Zetterberg, H.
- Affiliations
- University of Gothenburg (SE)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Kungälvs Sjukhus (SE)
- Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden
- Karolinska Institutet (SE)
- University of Oslo (NO)
- Lund University (SE)
- Corresponding author
- Mattsson, N
- ORCID
- Venue
- Multiple Sclerosis Journal
- Publisher
- SAGE Publications
- Published
- 2009-01-19
- Volume
- 15
- Issue
- 4
- Pages
- 448-454
- ISSN
- 1352-4585 (ISSN-L)
- 1477-0970
- OpenAlex
- W2115840666
- Cited by
- 61
- References
- 34
- Citations by year
- 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 8 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 8
- FWCI
- 6.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Multiple Sclerosis Journal (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- BACE1, beta-site APP-cleaving enzyme 1, multiple sclerosis, cerebrospinal fluid, amyloid precursor protein, amyloid-beta isoforms, systemic lupus erythematosus, brain involvement, myelination, disease severity, longitudinal follow-up
- MeSH terms
- Adult, Aged, Female, Humans, Lupus Erythematosus, Systemic, Male, Middle Aged, Multiple Sclerosis, Myelin Sheath, Nerve Regeneration, Peptide Fragments, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Amyloid Precursor Protein Secretases, Young Adult
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