{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T21:19:12Z","timestamp":1784236752112,"version":"3.55.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"name":"Intramural Research Program of the National Institutes of Neurological Disorder and Stroke"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis 4 (ALS4) are two forms of motor neuron disease characterized by clinically slow disease progression. Based on the current limited human studies, the contribution of central nervous neurodegeneration to these diseases and the rate of clinical progression is unclear. Neuronal proteins glial fibrillary acidic protein (GFAP), neurofilament light (NfL) chain, or Total-tau measured in either cerebrospinal fluid or blood could serve as sensitive markers of neurodegeneration. We studied 56 adult participants (32 SBMA, 7 ALS4, and 17 controls) who were enrolled at the National Institutes of Health, of whom 22 (10 SBMA, 7 ALS4, and 5 controls) underwent paired CSF and serum sampling, and of whom 6 participants were assessed longitudinally up to 24 months from initial visit. An additional 7 controls completed CSF sampling only. CSF GFAP, NfL chain, and Total-tau correlated with corresponding levels in serum (r = 0.74, r = 0.47, and r = 0.70, respectively). CSF GFAP was increased in patients with SBMA (median, 8840\u2005pg\/mL, interquartile range (IQR) 5780\u201310489) as compared to controls (median, 5315\u2005pg\/mL, IQR 1822\u20136657; P = 0.029) but not compared with ALS4 (median, 5015\u2005pg\/mL, IQR 3172\u20139803; P = 0.31). Patients with SBMA had increased concentrations of CSF NfL chain (median, 719\u2005pg\/mL, IQR 483\u2013773) as compared to ALS4 (median, 307\u2005pg\/mL, IQR 187\u2013629; P = 0.034) or controls (median, 395\u2005pg\/mL, IQR 307\u2013497; P = 0.024). In contrast, serum concentrations of either biomarker did not differ significantly between SBMA, ALS4, or controls. Higher CSF GFAP and NfL chain levels were associated with lower SBMA Functional Rating Scale scores (r = \u22120.49 and r = \u22120.42, respectively). Over the course of 24 months, the average change in SBMA Functional Rating Scale was \u22120.83 points, while the changes in CSF GFAP and NfL chain were progressive (increased 1.4-fold and 1.3-fold, respectively). Our data suggest that SBMA patients have increased concentrations of CSF GFAP and NfL chain as compared to ALS4 and controls, and higher levels of these biomarkers are associated with disease severity. Importantly, these results indicate that SBMA is associated with progressive neurodegeneration and that either CSF GFAP or NfL chain may be useful for patient stratification and monitoring treatment effects in clinical trials.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf275","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T11:32:02Z","timestamp":1753788722000},"source":"Crossref","is-referenced-by-count":3,"title":["CSF and blood neuronal injury biomarkers in spinal bulbar muscular atrophy and amyotrophic lateral sclerosis 4"],"prefix":"10.1093","volume":"7","author":[{"given":"Pashtun","family":"Shahim","sequence":"first","affiliation":[{"name":"Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]},{"name":"Department of Neurology, MedStar Georgetown University Hospital , Washington, DC 20007 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"AlQahtani","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela D","family":"Kokkinis","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narjis","family":"Kazmi","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Ezuma-Ngwu","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahan","family":"Misra","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Harmison","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Benoit","sequence":"additional","affiliation":[{"name":"Biospecimen Core, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Jones","sequence":"additional","affiliation":[{"name":"Biospecimen Core, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Howe","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice B","family":"Schindler","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galen O","family":"Joe","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Department, Clinical Center, NIH , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4994-2472","authenticated-orcid":false,"given":"Christopher","family":"Grunseich","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, NIH , 35 Convent Drive, Bethesda, MD 20814 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"issue":"7","key":"2025082607524474400_fcaf275-B1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1212\/WNL.18.7.671","article-title":"Progressive proximal spinal and bulbar muscular atrophy of late onset. 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