Ingannato Assunta, Bagnoli Silvia, Mazzeo Salvatore, Bessi Valentina, Matà Sabrina, Del Mastio Monica, Lombardi Gemma, Ferrari Camilla, Sorbi Sandro, Nacmias Benedetta
NEUROFARBA Department, University of Florence, Florence, Italy.
SOD Neurologia 1, Dipartimento Neuromuscolo-Scheletrico e Degli Organi di Senso, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
Front Neurosci. 2021 Sep 3;15:695049. doi: 10.3389/fnins.2021.695049. eCollection 2021.
To study the possible implication of the two biomarkers, intermediate alleles (IAs) of the Huntingtin (HTT) gene and neurofilament light chain (NfL) levels in plasma, in amyotrophic lateral sclerosis (ALS) patients.
We analyzed IAs in a cohort of 106 Italian ALS patients and measured the plasma NfL levels in 20% of the patients of the cohort. We correlated the two biomarkers with clinical phenotypes.
Intermediate alleles were present in 7.5% of the patients of our cohort, a frequency higher than that reported in general population. Plasma NfL levels increased with age at onset ( < 0.05). Patients with bulbar onset (BO) had higher plasma NfL concentration (CI -0.61 to -0.06, = 0.02) and a later age at onset of the disease (CI -24.78 to -4.93, = 0.006) with respect to the spinal onset (SO) form. Additionally, two of the patients, with IAs and plasma NfL concentration lower with respect to normal alleles' carriers, presented an age at onset higher than the mean of the entire cohort.
According to our findings, plasma NfL and IAs of HTT gene may represent potential biomarkers in ALS, providing evidence of a possible implication in clinical phenotype.
研究亨廷顿蛋白（HTT）基因的中间等位基因（IAs）和血浆神经丝轻链（NfL）水平这两种生物标志物在肌萎缩侧索硬化症（ALS）患者中的潜在意义。
我们分析了106例意大利ALS患者队列中的IAs，并测量了该队列中20%患者的血浆NfL水平。我们将这两种生物标志物与临床表型进行了关联分析。
我们队列中的患者有7.5%存在中间等位基因，这一频率高于一般人群中的报道。血浆NfL水平随发病年龄增加而升高（P<0.05）。与脊髓型起病（SO）形式相比，延髓型起病（BO）的患者血浆NfL浓度更高（置信区间为-0.61至-0.06，P = 0.02），且疾病发病年龄更晚（置信区间为-24.78至-4.93，P = 0.006）。此外，两名携带IAs且血浆NfL浓度低于正常等位基因携带者的患者，其发病年龄高于整个队列的平均水平。
根据我们的研究结果，血浆NfL和HTT基因的IAs可能代表ALS中的潜在生物标志物，为其在临床表型中的可能作用提供了证据。
