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Neurology. 2018 Jan 23;90(4):e273-e281. doi: 10.1212/WNL.0000000000004859. Epub 2017 Dec 27.

CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP.

Author information

1
From the Memory and Aging Center, Department of Neurology (J.C.R., R.M.T., G.D.R., B.L.M., A.L.B.), and Department of Epidemiology and Biostatistics, Division of Biostatistics (I.V.L.), University of California, San Francisco; and Department of Neurology (J.B.), Johns Hopkins University School of Medicine, Baltimore, MD. jrojasmartinez@memory.ucsf.edu.
2
From the Memory and Aging Center, Department of Neurology (J.C.R., R.M.T., G.D.R., B.L.M., A.L.B.), and Department of Epidemiology and Biostatistics, Division of Biostatistics (I.V.L.), University of California, San Francisco; and Department of Neurology (J.B.), Johns Hopkins University School of Medicine, Baltimore, MD.

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.

PMID:
29282336
PMCID:
PMC5798651
DOI:
10.1212/WNL.0000000000004859
[Indexed for MEDLINE]
Free PMC Article

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