{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T20:08:28Z","timestamp":1781813308470,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["ZIA HD008988"],"award-info":[{"award-number":["ZIA HD008988"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["ZIA HD008989"],"award-info":[{"award-number":["ZIA HD008989"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015411","name":"Ara Parseghian Medical Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Niemann\u2010Pick disease, type C1 (NPC1) is an inborn error of intracellular cholesterol transport. Impaired function of NPC1 leads to endolysosomal accumulation of unesterified cholesterol, which results in progressive neurodegeneration. Although the age of onset is variable, classical NPC1 is a pediatric disease. Identification of biomarkers that correlate with clinical phenotype and respond to therapeutic interventions will be essential for developing effective therapeutic interventions. A\u03b2 peptides and Tau protein are primary components of amyloid plaques and neurofibrillary tangles, respectively, which are major pathological features in neurodegenerative disorders. Cerebrospinal fluid (CSF) levels of total Tau, a biomarker of axonal damage, were elevated ~3\u2010fold (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) in 106 individuals with Niemann\u2010Pick disease, type C1, relative to age\u2010appropriate comparison samples. Baseline CSF total Tau levels correlated with clinical measures of disease severity. Specifically, CSF total Tau levels decreased with increased age of neurological onset (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>s<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u2009\u22120.42, FDR adj.\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and increased with increased Annual Severity Increment Score (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>s<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20090.52, FDR adj.\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Baseline CSF total Tau levels were decreased 40% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0066) in individuals being treated with miglustat, and longitudinal analysis substantiated this observation with a 40% decrease (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001, 95% CI 32%\u201347.4%). Longitudinal analysis also showed a significant (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.004) decrease of 19% (95% CI 7%\u201330%) in total Tau levels associated with intrathecal 2\u2010hydroxypropyl\u2010\u03b2\u2010cyclodextrin therapy. These data show that CSF total Tau levels are significantly increased in individuals with NPC1, positively correlated with increased disease severity, and respond to therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70016","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T20:10:12Z","timestamp":1741723812000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Elevated Cerebrospinal Fluid Total Tau in Niemann\u2010Pick Disease Type\n                    <scp>C1<\/scp>\n                    : Correlation With Clinical Severity and Response to Therapeutic Interventions"],"prefix":"10.1002","volume":"48","author":[{"given":"Niamh X.","family":"Cawley","sequence":"first","affiliation":[{"name":"Section on Molecular Dysmorphology, Division of Translational Medicine <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Applied and Computational Mathematics and Statistics University of Notre Dame  Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Farhat","sequence":"additional","affiliation":[{"name":"Section on Molecular Dysmorphology, Division of Translational Medicine <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Iben","sequence":"additional","affiliation":[{"name":"Molecular Genomics Core <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek M.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Section on Molecular Dysmorphology, Division of Translational Medicine <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Luke","sequence":"additional","affiliation":[{"name":"Section on Molecular Dysmorphology, Division of Translational Medicine <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron J.","family":"Padilla","sequence":"additional","affiliation":[{"name":"Section on Molecular Dysmorphology, Division of Translational Medicine <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hibaaq O.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Section on Molecular Dysmorphology, Division of Translational Medicine <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsolya K.","family":"Albert","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Neurological Sciences, and Anatomy and Cell Biology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendall P.","family":"Robbins","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Neurological Sciences, and Anatomy and Cell Biology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar","family":"Rahhal","sequence":"additional","affiliation":[{"name":"Section on Molecular Dysmorphology, Division of Translational Medicine <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An Dang","family":"Do","sequence":"additional","affiliation":[{"name":"Unit on Cellular Stress in Development and Diseases, Division of Translational Medicine <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Berry\u2010Kravis","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Neurological Sciences, and Anatomy and Cell Biology Rush University Medical Center  Chicago 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