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Whereas sNfL has robust literature, systematic studies on sNfH are lacking. Here, we aimed to assess the diagnostic value of sNfH in comparison to sNfL in a broad range of neurodegenerative disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured with immunoassays sNfH and sNfL in patients recruited in the multicenter German Frontotemporal Lobar Degeneration (FTLD) Consortium (n\u2009=\u2009340) and in a single-center German cohort (n\u2009=\u2009290). We assessed the diagnostic accuracy of serum biomarkers for ALS and dementia subtypes and their relationship with cognitive impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>sNfH and sNfL were significantly increased in ALS (n\u2009=\u200990) vs. controls (n\u2009=\u2009109) and ALS mimics (n\u2009=\u200956, p\u2009&lt;\u20090.001), with sNfL showing higher discriminative accuracy (AUC\u2009=\u20090.94\u20130.95) than sNfH (AUC\u2009=\u20090.87\u20130.88). sNfH\/sNfL ratio did not improve the diagnostic performance. Both markers were elevated in patients with dementia (n\u2009=\u2009289) vs. controls (p\u2009&lt;\u20090.001). sNfL was higher in behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA) and Creutzfeldt-Jakob disease (CJD) than in Alzheimer\u2019s disease (AD), whereas sNfH was similar in AD, PPA and bvFTD. sNfL, but not sNfH, was correlated with cognitive impairment at baseline\u00a0and cognitive decline at follow-up\u00a0in AD and bvFTD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>sNfH and sNfL are elevated in motoneuron and dementia disorders. sNfH showed good discriminative accuracy for ALS, which was slightly lower than that of sNfL. sNfL, but not sNfH, showed prognostic value for assessing\u00a0cognitive decline\u00a0in dementia.<\/jats:p>\n                  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(20059CB), ALS Association\/ALS Finding A Cure (24-SGP-691, 23-PPG-674\u20132), Charcot Foundation (D.7090), DZNE Innovation-to-Application (I2A_call7_Oeckl, I2A_call9_Oeckl), Cure Alzheimer\u00b4s Fund (together with MO) and consulting fees from LifeArc and Fundamental Pharma. VS received compensation for consulting services and\/or speaking activities from AveXis, Cytokinetics, Italfarmaco, Liquidweb S.r.l., Novartis Pharma AG, Amylyx Pharmaceuticals, Biogen, and Zambon Biotech SA; receives or has received research supports from the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call. He is in the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Diseases, Frontiers in Neurology, and Exploration of Neuroprotective Therapy. NT received compensation for consulting services and\/or speaking activities from Amylyx Pharmaceuticals, Biogen, Italfarmaco, Lundbeck and Zambon Biotech SA. The other authors have nothing to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"356"}}