• Lucas Hendrik Overeem, Bianca Raffaelli, Robert Fleischmann, Marie Süße, Antje Vogelgesang, Aleksandra Maleska Maceski, Athina Papadopoulou, Klemens Ruprecht, Wendy Su, Mirja Koch, Anke Siebert, Michal Arkuszewski, Nadia Tenenbaum, Jens Kuhle, and Uwe Reuter.
• Department of Neurology With Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany.
• J Headache Pain. 2023 Sep 19; 24 (1): 130130.

BackgroundMigraine is a disorder associated with neuropeptide release, pain and inflammation. Tau protein has recently been linked to inflammatory diseases and can be influenced by neuropeptides such as CGRP, a key neurotransmitter in migraine. Here, we report serum concentrations of total-tau protein in migraine patients and healthy controls.MethodsIn this cross-sectional study, interictal blood samples from n = 92 patients with episodic migraine (EM), n = 93 patients with chronic migraine (CM), and n = 42 healthy matched controls (HC) were studied. We assessed serum total-tau protein (t-tau) and for comparison neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L (UCH-L1) concentrations using the Neurology 4-plex kit, on a single molecule array HD-X Analyzer (Quanterix Corp Lexington, MA). Matched serum/cerebrospinal fluid (CSF) samples were used for post-hoc evaluations of a central nervous system (CNS) source of relevant findings. We applied non-parametric tests to compare groups and assess correlations.ResultsSerum t-tau concentrations were elevated in EM [0.320 (0.204 to 0.466) pg/mL] and CM [0.304 (0.158 to 0.406) pg/mL] patients compared to HC [0.200 (0.114 to 0.288) pg/mL] (p = 0.002 vs. EM; p = 0.025 vs. CM). EM with aura [0.291 (0.184 to 0.486 pg/mL); p = 0.013] and EM without aura [0.332 (0.234 to 0.449) pg/mL; p = 0.008] patients had higher t-tau levels than HC but did not differ between each other. Subgroup analysis of CM with/without preventive treatment revealed elevated t-tau levels compared to HC only in the non-prevention group [0.322 (0.181 to 0.463) pg/mL; p = 0.009]. T-tau was elevated in serum (p = 0.028) but not in cerebrospinal fluid (p = 0.760). In contrast to t-tau, all proteins associated with cell damage (NfL, GFAP, and UCH-L1), did not differ between groups.DiscussionMigraine is associated with t-tau elevation in serum but not in the CSF. Our clinical study identifies t-tau as a new target for migraine research.© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.

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