Highlights
- •CSF BACE1 levels are associated with depression and worse visual-spatial memory performance in RR-MS patients.
- •Higher levels of BACE1 correlate with worse prognosis and disease course of RR-MS patients.
- •BACE1 influences a group of neuroinflammatory mediators in RR-MS.
- •BACE1 is involved in mitochondrial dysfunction and oxidative stress mechanisms at the basis of MS pathophysiology.
- •BACE1 CSF levels correlate with neurodegenerative biomarkers including p-Tau and Aβ 1-42/1-40 ratio, a biomarker of Aβ pathology burden.
Abstract
Neurodegenerative and inflammatory processes influence the clinical course of multiple
sclerosis (MS). The β-site amyloid precursor protein cleaving enzyme 1 (BACE1) has
been associated with cognitive dysfunction, amyloid deposition and neuroinflammation
in Alzheimer's disease.
We explored in a group of 50 patients with relapsing-remitting MS the association
between the cerebrospinal fluid (CSF) levels of BACE1, clinical characteristics at
the time of diagnosis and prospective disability after three-years follow-up. In addition,
we assessed the correlations between the CSF levels of BACE 1, amyloid β (Aβ) 1-40
and 1-42, phosphorylated tau (pTau), lactate, and a set of inflammatory and anti-inflammatory
molecules.
BACE1 CSF levels were correlated positively with depression as measured with Beck
Depression Inventory–Second Edition scale, and negatively with visuospatial memory
performance evaluated by the Brief Visuospatial Memory Test-Revised. In addition,
BACE CSF levels were positively correlated with Bayesian Risk Estimate for MS at onset,
and with Expanded Disability Status Scale score assessed three years after diagnosis.
Furthermore, a positive correlation was found between BACE1, amyloid β 42/40 ratio
(Spearman's r = 0.334, p = 0.018, n = 50), pTau (Spearman's r = 0.304, p = 0.032,
n = 50) and lactate concentrations (Spearman's r = 0.361, p = 0.01, n = 50). Finally,
an association emerged between BACE1 CSF levels and a group of pro and anti-inflammatory
molecules, including interleukin (IL)-4, IL-17, IL-13, IL-9 and interferon-γ.
BACE1 may have a role in different key mechanisms such as neurodegeneration, oxidative
stress and inflammation, influencing mood, cognitive disorders and disability progression
in MS.
Keywords
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Article info
Publication history
Published online: January 23, 2023
Accepted:
January 18,
2023
Received in revised form:
January 11,
2023
Received:
December 17,
2022
Identification
Copyright
© 2023 Published by Elsevier B.V.
