Elevated Cerebrospinal Fluid Total Tau in Niemann‐Pick Disease Type C1: Correlation With Clinical Severity and Response to Therapeutic Interventions

• DOI: 10.1002/jimd.70016
• Publication Date: 2025-03-12T00:10:12Z
• Authors: Niamh X. Cawley; Ruyu Zhou; Nicole M. Farhat; James Iben; Derek M. Alexander; Rachel A. Luke; Cameron J. Padilla; Hibaaq O. Mohamed; Orsolya K. Albert; Kendall P. Robbins; Samar Rahhal; An Dang Do; Elizabeth Berry‐K...; Stephanie M. Cologna; Fang Liu; Forbes D. Porter
• Keywords: NPC1; Pathophysiology; Niemann–Pick disease

ABSTRACT Niemann‐Pick disease, type C1 (NPC1) is an inborn error of intracellular cholesterol transport. Impaired function NPC1 leads to endolysosomal accumulation unesterified cholesterol, which results in progressive neurodegeneration. Although the age onset variable, classical a pediatric disease. Identification biomarkers that correlate with clinical phenotype and respond therapeutic interventions will be essential for developing effective interventions. Aβ peptides Tau protein are primary components amyloid plaques neurofibrillary tangles, respectively, major pathological features neurodegenerative disorders. Cerebrospinal fluid (CSF) levels total Tau, biomarker axonal damage, were elevated ~3‐fold ( p < 0.0001) 106 individuals C1, relative age‐appropriate comparison samples. Baseline CSF correlated measures disease severity. Specifically, decreased increased neurological r s = −0.42, FDR adj. Annual Severity Increment Score 0.52, 0.0001). 40% 0.0066) being treated miglustat, longitudinal analysis substantiated this observation decrease 0.0001, 95% CI 32%–47.4%). Longitudinal also showed significant 0.004) 19% (95% 7%–30%) associated intrathecal 2‐hydroxypropyl‐β‐cyclodextrin therapy. These data show significantly NPC1, positively severity,