Bruno Antonio, Dolcetti Ettore, Azzolini Federica, Buttari Fabio, Gilio Luana, Iezzi Ennio, Galifi Giovanni, Borrelli Angela, Furlan Roberto, Finardi Annamaria, Carbone Fortunata, De Vito Francesca, Musella Alessandra, Guadalupi Livia, Mandolesi Georgia, Matarese Giuseppe, Centonze Diego, Stampanoni Bassi Mario
IRCSS Neuromed, Pozzilli, Italy.
Clinical Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Mult Scler Relat Disord. 2023 Mar;71:104528. doi: 10.1016/j.msard.2023.104528. Epub 2023 Jan 24.
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.
神经退行性变和炎症过程会影响多发性硬化症（MS）的临床病程。β-淀粉样前体蛋白裂解酶1（BACE1）与阿尔茨海默病中的认知功能障碍、淀粉样蛋白沉积和神经炎症有关。我们在一组50例复发缓解型MS患者中，探讨了脑脊液（CSF）中BACE1水平、诊断时的临床特征与三年随访后的预期残疾之间的关联。此外，我们评估了CSF中BACE1水平与淀粉样β蛋白（Aβ）1-40和1-42、磷酸化tau蛋白（pTau）、乳酸以及一组炎症和抗炎分子之间的相关性。BACE1的CSF水平与用贝克抑郁量表第二版测量的抑郁呈正相关，与用修订版简明视觉空间记忆测试评估的视觉空间记忆表现呈负相关。此外，BACE的CSF水平与MS发病时的贝叶斯风险估计以及诊断三年后评估的扩展残疾状态量表评分呈正相关。此外，还发现BACE1与淀粉样β蛋白42/40比值（斯皮尔曼相关系数r = 0.334，p = 0.018，n = 50）、pTau（斯皮尔曼相关系数r = 0.304，p = 0.032，n = 50）和乳酸浓度（斯皮尔曼相关系数r = 0.361，p = 0.01，n = 50）呈正相关。最后，BACE1的CSF水平与一组促炎和抗炎分子之间出现了关联，包括白细胞介素（IL）-4、IL-17、IL-13、IL-9和干扰素-γ。BACE1可能在神经退行性变、氧化应激和炎症等不同关键机制中发挥作用，影响MS患者的情绪、认知障碍和残疾进展。
