Cited by 61Multiple Sclerosis Research StudiesAlzheimer's disease research and treatmentsLysosomal Storage Disorders Research

Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis

Mattsson, N, Axelsson, M, Haghighi, S, Malmeström, C, Wu, G, Anckarsäter, R, Sankaranarayanan, S, Andreasson, U +13 more·2009·Multiple Sclerosis Journal

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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Crossref · 10.1177/1352458508100031

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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
Venue
Multiple Sclerosis Journal
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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