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Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden niklas.mattsson{at}neuro.gu.se

M Axelsson

Institute of Neuroscience and Physiology, Department of Neurology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

S Haghighi

Institute of Neuroscience and Physiology, Department of Neurology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

C Malmeström

Institute of Neuroscience and Physiology, Department of Neurology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

G Wu

Alzheimer’s Research, Merck Research Laboratories, West Point, PA, USA

R Anckarsäter

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Department of Anaesthesiology and Intensive Care, Kungälv Hospital, Kungälv, Sweden

S Sankaranarayanan

Alzheimer’s Research, Merck Research Laboratories, West Point, PA, USA

U Andreasson

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden

S Fredrikson

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

A Gundersen

University of Oslo, Department of Neurology at Akershus University Hospital, Norway

L Johnsen

University of Oslo, Department of Neurology at Akershus University Hospital, Norway

T Fladby

University of Oslo, Department of Neurology at Akershus University Hospital, Norway

A Tarkowski

Department of Rheumatology and Inflammation Research, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

E Trysberg

Department of Rheumatology, Karolinska Institutet, Stockholm, Sweden

A Wallin

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden

H Anckarsäter

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Institute for Clinical Sciences, Malmö University Hospital, Lund University, Sweden

J Lycke

Institute of Neuroscience and Physiology, Department of Neurology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

O Andersen

Institute of Neuroscience and Physiology, Department of Neurology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

AJ Simon

Alzheimer’s Research, Merck Research Laboratories, West Point, PA, USA

K Blennow

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden

H Zetterberg

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden

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.

Key Words: BACE1 • cerebrospinal fluid • multiple sclerosis • myelination • neuroinflammation • systemic lupus erythematosus

This version was published on April 1, 2009

Multiple Sclerosis, Vol. 15, No. 4, 448-454 (2009)
DOI: 10.1177/1352458508100031


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