| Title: |
CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP |
| Authors: |
Rojas, Julio C; Bang, Jee; Lobach, Iryna V; Tsai, Richard M; Rabinovici, Gil D; Miller, Bruce L; Boxer, Adam L; Williams, David; Lafontaine, Anne Louise; Marras, Connie; Jog, Mandar; Panisset, Michael; Lang, Anthony; Parker, Lesley; Stewart, Alistair J; Corvol, Jean-Christophe; Azulay, Jean-Philippe; Couratier, Philippe; Mollenhauer, Brit; Lorenzl, Stefan; Ludolph, Albert; Benecke, Reiner; Hoglinger, Gunter; Lipp, Axel; Reichmann, Heinz; Woitalla, Dirk; Chan, Dennis; Zermansky, Adam; Burn, David; Lees, Andrew; Gozes, Illana; Boxer, Adam; Roberson, Erik; Honig, Lawrence; Zamrini, Edward; Pahwa, Rajesh; Bordelon, Yvette; Driver-Dunkley, Erika; Lessig, Stephanie; Lew, Mark; Womack, Kyle; Boeve, Brad; Ferrara, Joseph; Hillis, Argyle; Kaufer, Daniel; Kumar, Rajeev; Xie, Tao; Gunzler, Steven; Zesiewicz, Theresa; Dayalu, Praveen; Golbe, Lawrence; Grossman, Murray; Jankovic, Joseph; McGinnis, Scott; Santiago, Anthony; Tuite, Paul; Isaacson, Stuart; Leegwater-Kim, Julie; Litvan, Irene; Knopman, David S; Schneider, Lon S; Doody, Rachelle S; Koestler, Mary; Jack, Clifford R; Van Deerlin, Viviana; Randolph, Christopher; Whitaker, Steve; Hirman, Joe; Gold, Michael; Morimoto, Bruce H |
| Source: |
Neurology, vol 90, iss 4 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2018 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3209 Neurosciences (for-2020); 3202 Clinical Sciences (for-2020); Rare Diseases (rcdc); Frontotemporal Dementia (FTD) (rcdc); Alzheimer's Disease Related Dementias (ADRD) (rcdc); Clinical Research (rcdc); Neurosciences (rcdc); Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) (rcdc); Brain Disorders (rcdc); Neurodegenerative (rcdc); Aging (rcdc); Alzheimer's Disease (rcdc); Acquired Cognitive Impairment (rcdc); Dementia (rcdc); 4.1 Discovery and preclinical testing of markers and technologies (hrcs-rac); 2.1 Biological and endogenous factors (hrcs-rac); Neurological (hrcs-hc); Aged (mesh); Amyloid beta-Peptides (mesh); Biomarkers (mesh); Brain (mesh); Central Nervous System Agents (mesh); Disease Progression (mesh); Double-Blind Method (mesh); Female (mesh); Humans (mesh); Longitudinal Studies (mesh); Male (mesh); Neurofilament Proteins (mesh) |
| Subject Geographic: |
e273 - e281 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt0f768937; https://escholarship.org/uc/item/0f768937; https://escholarship.org/content/qt0f768937/qt0f768937.pdf |
| DOI: |
10.1212/wnl.0000000000004859 |
| Availability: |
https://escholarship.org/uc/item/0f768937; https://escholarship.org/content/qt0f768937/qt0f768937.pdf; https://doi.org/10.1212/wnl.0000000000004859 |
| Rights: |
public |
| Accession Number: |
edsbas.2AB0F81C |
| Database: |
BASE |