Journal
NEURON
Volume 91, Issue 1, Pages 56-66Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2016.05.018
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Funding
- MetLife Foundation, New York
- ECTRIMS Research Fellowship Program, University of Basel
- Swiss MS Society
- Swiss National Research Foundation
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A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (alpha-synuclein, Tau, A beta). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of alpha-synucleinopathies, tauopathy, and beta-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of alpha-synuclein lesions increased CSF and blood NfL levels, while blocking Ab lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human alpha-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases.
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