TY - JOUR
T1 - CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP
AU - Rojas, Julio C.
AU - Bang, Jee
AU - Lobach, Iryna V.
AU - Tsai, Richard M.
AU - Rabinovici, Gil D.
AU - Miller, Bruce L.
AU - Boxer, Adam L.
N1 - Funding Information:
Supported by R01AG038791, U54NS092089, T32 AG23481, and the Tau Consortium.
Funding Information:
J. Rojas, J. Bang, I. Lobach, and R. Tsai report no disclosures relevant to the manuscript. G. Rabinovici served on the Roche, Lundbeck, and Piramidal scientific advisory boards. He received travel or funding honoraria from GE Healthcare, Piramidal Imaging, the Alzheimer’s Association, the American Academy of Neurology, Eisai, and Roche and consultant fees from Putnam. He receives research support from Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, Piramal, NIH/NIA R01-AG04561, P50-AG02350 and R01-AG048234, NIH/National Institute of Neurological Disorders and Stroke U54NS092089 and R01-AG03879, Alzheimer’s Association, John Douglas French Alzheimer’s Foundation, Hellman Family Foundation, Tau Consortium, American College of Radiology, Association for Frontotemporal Lobar Degeneration, and Michael J. Fox Foundation. B. Miller served on the Tau Consortium, Douglas French Foundation, Larry Hillblom Foundation, and SAB Nat’l Institute for Health Research in Dementia advisory boards. He is an external advisor for the Stanford University and Pittsburgh Alzheimer’s Disease research centers. He is on the editorial boards of Neurocase, Cambridge University Press, and Guilford Publications, Inc. He receives publishing royalties for Behavioral Neurology of Dementia (Cambridge 2009), Handbook of Neurology (Elsevier 2009), and The Human Frontal Lobes (Guilford, 2008). He receives research support from NIA P50 AG23501 P01 AG19724, P50 AG16573, and CMS 1C1CMS331346-01-00. A. Boxer receives research support from NIH U54NS092089, R01AG031278, R01AG038791, R01AG032306, R01AG022983, the Tau Research Consortium, the Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, and the Alzheimer’s Association. He has served as a consultant for AbbVie, Cellgener, Ionis, Janssen, and Merck, and received research support from Avid, Biogen, BMS, C2N, Cortice, Forum, Genentech, Janssen, Pfizer, Eli Lilly, Roche, and TauRx. He holds stock options in Alector and Delos. Go to Neurology.org/N for full disclosures.
Funding Information:
Funding for this study was obtained via NIH/NIA grants and the Tau Consortium. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© 2018 American Academy of Neurology
PY - 2018/1/23
Y1 - 2018/1/23
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0000000000004859
DO - 10.1212/WNL.0000000000004859
M3 - Article
C2 - 29282336
AN - SCOPUS:85046342518
SN - 0028-3878
VL - 90
SP - E273-E281
JO - Neurology
JF - Neurology
IS - 4
ER -