Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis.
BACKGROUND
Cell and animal experiments have shown that beta-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-beta (Abeta) 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.
Mattsson
N
N
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden. niklas.mattsson@neuro.gu.se
Axelsson
M
M
Haghighi
S
S
Malmeström
C
C
Wu
G
G
Anckarsäter
R
R
Sankaranarayanan
S
S
Andreasson
U
U
Fredrikson
S
S
Gundersen
A
A
Johnsen
L
L
Fladby
T
T
Tarkowski
A
A
Trysberg
E
E
Wallin
A
A
Anckarsäter
H
H
Lycke
J
J
Andersen
O
O
Simon
A J
AJ
Blennow
K
K
Zetterberg
H
H
D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D016282:Aspartic Acid Endopeptidases / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D055815:Young Adult
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human