| Summary: | Early detection of <i>cis</i> phosphorylated tau (<i>cis</i> P-tau) may help as an effective treatment to control the progression of Alzheimer’s disease (AD). Recently, we introduced for the first time a monoclonal antibody (mAb) with high affinity against <i>cis</i> P-tau. In this study, the <i>cis</i> P-tau mAb was utilized to develop a label-free immunosensor. The antibody was immobilized onto a gold electrode and the electrochemical responses to the analyte were acquired by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV). The immunosensor was capable of selective detection of <i>cis</i> P-tau among non-specific targets like <i>trans</i> P-tau and major plasma proteins. A wide concentration range (10 × 10<sup>−14</sup> M–3.0 × 10<sup>−9</sup> M) of <i>cis</i> P-tau was measured in PBS and human serum matrices with a limit of detection of 0.02 and 0.05 pM, respectively. Clinical applicability of the immunosensor was suggested by its long-term storage stability and successful detection of <i>cis</i> P-tau in real samples of cerebrospinal fluid (CSF) and blood serum collected from human patients at different stages of AD. These results suggest that this simple immunosensor may find great application in clinical settings for early detection of AD which is an unmet urgent need in today’s healthcare services.
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