Tauopathies are leading cause of loss of autonomy in the elderly, implying a progressive cognitive decline. There is not an effective treatment early diagnosis of tauopathies. We propose an in-vitro and theragnostic approach by using a novel phosphorylated Tau(p-Tau) monoclonal antibody(mAb) responsible for tau self-aggregation and regulation.A diagnostic Sandwich ELISA kit was developed and tested in 89 cerebrospinal fluid (CSF) samples of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients for detection of p-Tau.The proof of concept study reported specific signals above the limit of detection while maintaining a low intra-assay coefficient of variation and the levels of the isoforms of tau showed the same behaviour with an increase in CSF as the disease progresses.Also,the p-Tau mAb was intraventricularly administered to transgenic mice models of tauopathy and we observed its effect on behaviour and brain functionality. The results showed that 4-week treatment of p-Tau mAb, a reduction of p-Tau levels in the cortex and hippocampus and an improved of motor outcome by delaying the hindlimb clasping and latency to fall in the rotarod test. Moreover,p-Tau mAb was radiolabelled with 89Zr and the results in transgenic mice showed that the mAb-89Zr were stable in circulation up to 10 days, but the amount reaching the brain was <0.2%. These results showed a novel theragnostic p-Tau mAb that recognizes an early biomarker of p-Tau in AD patients. Therefore, multicenter clinical trials are necessary to validate these promising results and it is imperative increase the amount of mAb that reaches the brain.