CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP. (23rd January 2018)

• Record Type: Journal Article
• Authors: Rojas, Julio C.; Bang, Jee; Lobach, Iryna V.; Tsai, Richard M.; Rabinovici, Gil D.; Miller, Bruce L.; Boxer, Adam L.
• Is Part Of: Neurology. Volume 90:Number 4(2018)
• Publication Date: 2018-01-23
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000004859
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To determine the ability of CSF biomarkers to predict disease progression in progressive supranuclear palsy (PSP). Methods: We compared the ability of baseline CSF β-amyloid1–42, tau, phosphorylated tau 181 (p-tau), and neurofilament light chain (NfL) concentrations, measured by INNO-BIA AlzBio3 or ELISA, to predict 52-week changes in clinical (PSP Rating Scale [PSPRS] and Schwab and England Activities of Daily Living [SEADL]), neuropsychological, and regional brain volumes on MRI using linear mixed effects models controlled for age, sex, and baseline disease severity, and Fisher F density curves to compare effect sizes in 50 patients with PSP. Similar analyses were done using plasma NfL measured by single molecule arrays in 141 patients. Results: Higher CSF NfL concentration predicted more rapid decline (biomarker × time interaction) over 52 weeks in PSPRS ( p = 0.004, false discovery rate–corrected) and SEADL ( p = 0.008), whereas lower baseline CSF p-tau predicted faster decline on PSPRS ( p = 0.004). Higher CSF tau concentrations predicted faster decline by SEADL ( p = 0.004). The CSF NfL/p-tau ratio was superior for predicting change in PSPRS, compared to p-tau ( p = 0.003) or NfL ( p = 0.001) alone. Higher NfL concentrations in CSF or blood were associated with greater superior cerebellar peduncle atrophy (fixed effect, p ⩽ 0.029 and 0.008, respectively). Conclusions: Both CSF p-tau and NfL correlate with disease severity and rate of disease progression in PSP. The inverse correlation of p-tau with disease severity suggests a potentially different mechanism of tau pathology in PSP as compared to Alzheimer disease.