NEFL and neurodegenerative disease: The appearance of the neuron-specific NF-L filament protein in biofluid compartments outside of the neuron is: (i) an overall signal for the inception of the functional decline of large CNS neurons; (ii) the quantifiable abundance of NF-L in multiple biofluids appears to be an indicator of the degree of this neurodegeneration in both the CNS and/or PNS; and (iii) while absolute NF-L abundances are diagnostically useful NF-L presence alone does not appear to be a selective biomarker for any specific neurodegenerative disease.