Figure 1.

Conceptual representation of NfL in the brain and CSF, where cNFL_Brain (dense pattern) and cNFL_CSF (light pattern) indicate the concentrations of NfL in brain tissue and CSF, respectively. V_Brain is the volume of brain tissue, V_CSF is the volume in the CSF compartment and t is the time variable, which is also equivalent to age in the model. –dV_Brain/dt is the negative rate of change of the brain volume; the negative sign expresses this as a positive rate of neurodegeneration. Flow into and out of the CSF compartment is denoted CSF_Flow. The observed NfL concentration in CSF can change due to alterations in the rate of neurodegeneration (NfL input to CSF) or CSF_Flow (NfL elimination from CSF). The latter is physiologically equivalent to CSF clearance, denoted CL_NfL.