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 (a-synuclein, Tau, Ab). 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 a-synucleinopathies,
tauopathy, and b-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 a-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
a-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.