Autoantibodies to neuronal antigens are viewed as potential biomarkers for neurodegenerative diseases. Increasing evidence, however, suggests a dissociation of the neurodegenerative process in the central nervous system and dynamics of neuronal proteins in peripheral circulation with prevalence of a wide variety of immunoglobulins reactive to neuronal antigens reported also in the blood of healthy subjects, including children.
Recently discovered physiological turnover of neurons in enteric nervous system with release of neuronal proteins in circulation may account for this conundrum and provide a new perspective on molecular biomarkers of neurodegenerative diseases and immunotherapy.