AbstractIridium oxide nanoparticles (IrO2 NPs) synthesized following a previously reported chemical route are presented as novel tags for immunosensing taking advantage of their electrocatalytic activity towards water oxidation reaction (WOR). Cyclic voltammetry and chronoamperometry for the evaluation of the IrO2 NPs electrocatalytic activity towards WOR at neutral pH were used. The chronoamperometric current recorded at a fixed potential of +1.3 V constituted the analytical signal allowing the quantification of IrO2 NPs at nM levels. Modification of the surface of citrate‐capped IrO2 NPs with anti‐Apolipoprotein E antibodies (αApoE) was successfully achieved and the as‐prepared conjugates were used for the electrocatalytic detection of ApoE Alzheimer disease (AD) biomarker in a magnetosandwich immunoassay, reaching a detection limit of 68 ng/mL. Human plasma of a patient suffering AD was also evaluated, estimating an ApoE concentration of 20 µg/mL which is in concordance with the obtained in previously reported approaches. This novel IrO2 NPs based electrocatalytic assay presents the advantage of the signal generation in the same medium where the immunoassay takes place (PBS, pH 7.4) avoiding the use of additional reagents which also opens the way to future integrated biosensing systems and platforms with interest for other proteins as well as DNA and cells analysis.