米诺环素治疗会混淆将神经丝作为生物标志物的解读的证据。

Evidence that minocycline treatment confounds the interpretation of neurofilament as a biomarker.

作者信息

Gentile Juliana E, Heiss Christina N, Corridon Taylor L, Mortberg Meredith A, Fruhwürth Stefanie, Guzman Kenia, Grötschel Lana, Montoliu-Gaya Laia, Chan Kwan, Herring Neil C, Janicki Timothy, Nhass Rajaa, Manavala Sarathy Janani, Erickson Brian, Kunz Ryan, Erickson Alison, Braun Craig, Henry Katherine T, Bry Lynn, Arnold Steven E, Vallabh Minikel Eric, Zetterberg Henrik, Vallabh Sonia M

机构信息

Program in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal 431 80, Sweden.

出版信息

Brain Commun. 2025 May 23;7(3):fcaf175. doi: 10.1093/braincomms/fcaf175. eCollection 2025.

DOI:10.1093/braincomms/fcaf175

PMID:40417399

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12100619/

Abstract

Neurofilament light (NfL) concentration in CSF and blood serves as an important biomarker in neurology drug development. Changes in NfL are generally assumed to reflect changes in neuronal damage, while little is known about the clearance of NfL from biofluids. In a study of asymptomatic individuals at risk for prion disease, both blood and CSF NfL spiked in one participant following a 6-week course of minocycline, absent any other biomarker changes and without subsequent onset of symptoms. We subsequently observed high NfL after minocycline treatment in discarded clinical plasma samples from inpatients, in mouse plasma and in conditioned media from neuron-microglia co-cultures. The specificity and kinetics of NfL response lead us to hypothesize that minocycline does not cause or exacerbate neuronal damage, but instead affects NfL by inhibiting its clearance, posing a potential confounder for the interpretation of this important biomarker.

摘要

脑脊液和血液中的神经丝轻链（NfL）浓度是神经学药物研发中的一项重要生物标志物。人们普遍认为NfL的变化反映了神经元损伤的变化，然而对于NfL从生物流体中的清除情况却知之甚少。在一项针对有朊病毒病风险的无症状个体的研究中，一名参与者在接受为期6周的米诺环素治疗后，血液和脑脊液中的NfL均出现飙升，且没有任何其他生物标志物变化，也未随后出现症状。我们随后在住院患者废弃的临床血浆样本、小鼠血浆以及神经元-小胶质细胞共培养的条件培养基中观察到米诺环素治疗后NfL升高。NfL反应的特异性和动力学使我们推测，米诺环素不会导致或加重神经元损伤，而是通过抑制其清除来影响NfL，这对解释这一重要生物标志物构成了潜在的干扰因素。