Tau is a neuronal protein responsible for microtubule formation [1]. It is also the pathological protein active in the Alzheimer’s Disease (AD) pathway. When Tau begins to aggregate as a result of misfolding, the neuronal cells die due to the lack of microtubule formation and can take on prion-like properties [2]. Therefore, detection of aggregated Tau can serve as a powerful tool in the early diagnosis of AD and dementia related diseases. As has been previously demonstrated, Tau 441 can be detected with an electrochemical immunoassay based on the electrochemical impedance spectroscopy (EIS) by using gold electrode [3]. The EIS was also used to monitor interactions between Tau protein and Heparin [4]. Due to the sensitive nature of protein molecules, buffers of physiological pH need to be employed to maintain native protein structure. However, not all buffer solutions are appropriately suited for surface studies. Herein, we describe use of EIS to monitor and detect surface stability of Tau protein films on gold electrode in two common buffers: MES buffer and Phosphate Buffer (PB). Additionally, the stability of partial and complete surfaces was also monitored. The partial surface was completed by backfilling with a solution of bovine serum albumin (BSA) and the complete surface was backfilled using 1-butylamine and hexanethiol. After modifying the surface of the electrode with activated lipoic acid and Tau, a series of further incubation steps were performed to test surface stability under various conditions. The EIS was measured as a function of Tau or Heparin concentrations, and incubation time and temperature. The control experiments included, Tau-free surface, Heparin-free solution, and buffer solutions in order to minimize non-specific interactions. The stability of the surfaces was measured as a signal change in EIS after incubations and it was discovered that certain buffered solutions and partial surfaces induced large changes in tau protein films on surfaces.