Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases

A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). 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 α-synucleinopathies, tauopathy, and β-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 α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-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. •Increased NfL in CSF and blood of proteopathic neurodegenerative diseases•Increased NfL in CSF and blood coincides with onset of proteopathic lesions in brain•NfL as disease progression and treatment response marker•Translational value and predictability of current mouse models in clinical settings Bacioglu et al. (2016) report NfL increases in CSF and blood of murine models and human α-synucleinopathies, tauopathies, and β-amyloidosis. NfL in bodily fluid constitutes a biomarker of neurodegeneration reflecting the translational value and potential impact of current mouse models in clinical settings.