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Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising fluid biomarkers to support the diagnostic workup. Serum NfL is a marker of neuroaxonal decay sensitive to temporal changes, while elevated sGFAP levels may reflect astrocytal involvement in PPMS. We assessed sNfL and sGFAP levels in 25 patients with PPMS, 25 patients with SPG4 (the most common type of HSP) and 60 controls, using the highly sensitive single-molecule array (Simoa) platform. Patients were matched in age, sex, age at onset, disease duration and disease severity. Serum NfL levels were significantly increased in PPMS compared to SPG4 (p = 0.041, partial \u03b7\u00b2 = 0.088), and there was a trend toward relatively higher sGFAP levels in PPMS (p = 0.097). However, due to overlapping biomarker values in both groups, we did not find sNfL and sGFAP to be useful as differential biomarkers in our cohort. The temporal dynamics indicate sNfL and sGFAP levels are most markedly elevated in PPMS in earlier disease stages, supporting their investigation in this group most in need of a diagnostic biomarker.<\/jats:p>","DOI":"10.3390\/ijms232113466","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T03:28:10Z","timestamp":1667532490000},"page":"13466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers in Primary Progressive Multiple Sclerosis and Hereditary Spastic Paraplegia Type 4"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6211-903X","authenticated-orcid":false,"given":"Christoph","family":"Kessler","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Diseases, University of T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, Otfried-M\u00fcller-Str. 27, 72076 T\u00fcbingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Otfried-M\u00fcller-Str. 23, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9900-4295","authenticated-orcid":false,"given":"Christoph","family":"Ruschil","sequence":"additional","affiliation":[{"name":"Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, Otfried-M\u00fcller-Str. 27, 72076 T\u00fcbingen, Germany"},{"name":"Department of Neurology and Stroke, University of T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9731-4169","authenticated-orcid":false,"given":"Ahmed","family":"Abdelhak","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco (UCSF), 675 Nelson Rising Lane, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7250-8597","authenticated-orcid":false,"given":"Carlo","family":"Wilke","sequence":"additional","affiliation":[{"name":"Division Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of T\u00fcbingen, Otfried-M\u00fcller-Str. 27, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Maleska","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital and University of Basel, Petersgraben 4, 4031 Basel, Switzerland"},{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Spitalstr. 2, 4031 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Kuhle","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital and University of Basel, Petersgraben 4, 4031 Basel, Switzerland"},{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Spitalstr. 2, 4031 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Krumbholz","sequence":"additional","affiliation":[{"name":"Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, Otfried-M\u00fcller-Str. 27, 72076 T\u00fcbingen, Germany"},{"name":"Department of Neurology and Stroke, University of T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"Department of Neurology and Pain Treatment, Immanuel Klinik R\u00fcdersdorf, University Hospital of the Brandenburg Medical School Theodor Fontane, 15562 R\u00fcdersdorf bei Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus C.","family":"Kowarik","sequence":"additional","affiliation":[{"name":"Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, Otfried-M\u00fcller-Str. 27, 72076 T\u00fcbingen, Germany"},{"name":"Department of Neurology and Stroke, University of T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"Department of Neurology, Technische Universit\u00e4t M\u00fcnchen, Ismaninger Str. 22, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-2766","authenticated-orcid":false,"given":"Rebecca","family":"Sch\u00fcle","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases, University of T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, Otfried-M\u00fcller-Str. 27, 72076 T\u00fcbingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Otfried-M\u00fcller-Str. 23, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S1474-4422(07)70243-0","article-title":"Primary-progressive multiple sclerosis","volume":"6","author":"Miller","year":"2007","journal-title":"Lancet 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