BACE1 influences clinical manifestations and central inflammation in relapsing remitting multiple sclerosis

• DOI: 10.1016/j.msard.2023.104528
• Publication Date: 2023-01-24T01:54:44Z
• Authors: Antonio Bruno; Ettore Dolcetti; Federica Azzolini; Fabio Buttari; Luana Gilio; Ennio Iezzi; Giovanni Galifi; Angela Borrelli; Roberto Furlan; Annamaria Finardi; Fortunata Carbone; Francesca De Vito; Alessandra Musella; Livia Guadalupi; Georgia Mandolesi; Giuseppe Matarese; Diego Centonze; Mario Stampanoni ...
• Keywords: Inflammation; Amyloid beta-Peptides; Multiple Sclerosis; BACE1; CSF; Bayes Theorem; 3. Good health; Multiple sclerosis; Settore MED/26 - NEUROLOGIA; 03 medical and health sciences; Neurodegeneration, CSF; Multiple Sclerosis, Relapsing-Remitting; 0302 clinical medicine; Neuroinflammation; Humans; Aspartic Acid Endopeptidases; Prospective Studies; Neurodegeneration; Amyloid Precursor Protein Secretases; BACE1; Multiple sclerosis; Neurodegeneration, CSF; Neuroinflammation

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.