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To the Editor: We read with interest the article by Tokuda et al.,1 who studied CSF concentrations of oligomeric α-synuclein protein as a potential biomarker for Parkinson disease (PD).
Oligomers of α-synuclein were quantified by ELISA using the same capture and (biotinylated) detection monoclonal antibody directed against an α-synuclein epitope. Only oligomeric proteins that expose multiple epitopes for recognition by capture and detection antibodies were quantified. However, no monomeric proteins containing a single epitope and thus precluding binding of the detector antibody were quantified. Using this ELISA design, Tokuda et al. demonstrated an elevated ratio of α-synuclein oligomers/total α-synuclein in the CSF of patients with PD compared to normal controls.
Recently, it was demonstrated that heterophilic antibodies (HA) present in human body fluids may lead to false-positive results in this ELISA design.2 HA are polyreactive antibodies that recognize antibodies from another species and may crosslink the capture antibody with the detection antibody, which are both derived from the same species. This may lead to a positive signal in the oligomer ELISA in the absence of the target …
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