Neurofilament light chain and tau concentrations are markedly increased in the serum of patients with sporadic Creutzfeldt-Jakob disease, and tau correlates with rate of disease progression.

Abstract

OBJECTIVES:

A blood-based biomarker of neuronal damage in sporadic Creutzfeldt-Jakob disease (sCJD) will be extremely valuable for both clinical practice and research aiming to develop effective therapies.

METHODS:

We used an ultrasensitive immunoassay to measure two candidate biomarkers, tau and neurofilament light (NfL), in serum from patients with sCJD and healthy controls. We tested longitudinal sample sets from six patients to investigate changes over time, and examined correlations with rate of disease progression and associations with known phenotype modifiers.

RESULTS:

Serum concentrations of both tau and NfL were increased in patients with sCJD. NfL distinguished patients from controls with 100% sensitivity and 100% specificity. Tau did so with 91% sensitivity and 83% specificity. Both tau and NfL appeared to increase over time in individual patients, particularly in those with several samples tested late in their disease. Tau, but not NfL, was positively correlated with rate of disease progression, and was particularly increased in patients homozygous for methionine at codon 129 of PRNP.

CONCLUSIONS:

These findings independently replicate other recent studies using similar methods and offer novel insights. They show clear promise for these blood-based biomarkers in prion disease. Future work should aim to fully establish their potential roles for monitoring disease progression and response to therapies.

• Authors: Andrew Geoffrey Bourne Thompson, Connie Luk, Amanda J Heslegrave, Henrik Zetterberg, Simon H Mead, John Collinge, Graham S Jackson
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 89 Issue 9 Pg. 955-961 (09 2018) ISSN: 1468-330X [Electronic] England
• PMID: 29487167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chemical References

• Biomarkers
• Neurofilament Proteins
• neurofilament protein L
• tau Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Case-Control Studies
• Creutzfeldt-Jakob Syndrome (blood)
• Disease Progression
• Female
• Humans
• Male
• Middle Aged
• Neurofilament Proteins (blood)
• Sensitivity and Specificity
• tau Proteins (blood)