CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP
Citation Manager Formats
Make Comment
See Comments
![Loading Loading](https://n.neurology.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif)
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
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.
Glossary
- 4R=
- 4 microtubule binding repeat;
- Aβ42=
- β-amyloid1–42;
- AD=
- Alzheimer disease;
- CGI-S=
- Clinical Global Impression of Severity;
- CI=
- confidence interval;
- CTT1=
- color trails test 1;
- CTT2=
- color trails test 2;
- FDR=
- false discovery rate;
- LNS=
- letter-number sequencing;
- MMSE=
- Mini-Mental State Examination;
- NfL=
- neurofilament light chain;
- p-tau=
- phosphorylated tau 181;
- PSP=
- progressive supranuclear palsy;
- PSP-RS=
- progressive supranuclear palsy–Richardson syndrome;
- PSPRS=
- Progressive Supranuclear Palsy Rating Scale;
- RBANS=
- Repeatable Battery for the Assessment of Neuropsychological Disease Severity;
- SCP=
- superior cerebellar peduncle;
- SEADL=
- Schwab and England Activities of Daily Living
Footnotes
Coinvestigators are listed at links.lww.com/WNL/A150
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received May 30, 2017.
- Accepted in final form October 16, 2017.
- Copyright © 2017 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Dr. Mark Burish and Dr. Emmanuelle Schindler
► Watch
Related Articles
- No related articles found.
Topics Discussed
Alert Me
Recommended articles
-
Research
Neurofilament Light Chain Related to Longitudinal Decline in Frontotemporal Lobar DegenerationJiasi Vicky Zhang, David J. Irwin, Kaj Blennow et al.Neurology: Clinical Practice, September 04, 2020 -
Article
Blood-based NfLA biomarker for differential diagnosis of parkinsonian disorderOskar Hansson, Shorena Janelidze, Sara Hall et al.Neurology, February 08, 2017 -
Article
Serum NFL discriminates Parkinson disease from atypical parkinsonismsTainá M. Marques, Anouke van Rumund, Patrick Oeckl et al.Neurology, February 27, 2019 -
Articles
CSF neurofilament and glial fibrillary acidic protein in normal pressure hydrocephalusM. Tullberg, L. Rosengren, E. Blomsterwall et al.Neurology, April 01, 1998