Evidence that minocycline treatment confounds the interpretation of neurofilament as a biomarker.

Neurofilament light (NfL) concentration in CSF and blood serves as an important biomarker in neurology drug development. Changes in NfL are generally assumed to reflect changes in neuronal damage, while little is known about the clearance of NfL from biofluids. In a study of asymptomatic individuals at risk for prion disease, both blood and CSF NfL spiked in one participant following a 6-week course of minocycline, absent any other biomarker changes and without subsequent onset of symptoms. We subsequently observed high NfL after minocycline treatment in discarded clinical plasma samples from inpatients, in mouse plasma and in conditioned media from neuron-microglia co-cultures. The specificity and kinetics of NfL response lead us to hypothesize that minocycline does not cause or exacerbate neuronal damage, but instead affects NfL by inhibiting its clearance, posing a potential confounder for the interpretation of this important biomarker.