Review: Tau Biochemistry and Therapeutics in Alzheimer’ s Disease

Preface: The incidence of Alzheimer’s disease has been continuously increasing over the past two decades. This has significant implications to the quality of life of many individuals and their families, and also places a large financial burden on the healthcare system. The tau protein is unanimously one of the hallmark proteins implicated in Alzheimer’s disease. The function of tau in the neurons is to stabilize the structure of microtubules by binding along the full-length of the tubules. However, in AD, tau proteins on the microtubule are hyperphosphorylated, causing them to dissociate from the microtubule. As a result, microtubules fall apart, destabilizing the cytoskeleton, and eventually leading to the collapse and death of the affected neuron. In addition, the insoluble, dissociated tau proteins tend to aggregate with one another in the cytoplasm, leading to the formation of toxic structures known as neurofibrillary tangles (NFT). Neuronal collapse and NFT formation are two potent factors that cause neurodegeneration in AD. Therefore, because of tau’s critical role in underlying AD—as well as other neurodegenerative diseases commonly grouped as tauopathies—researchers along the past two decades have rigorously developed and tested a wide array of tau-targeted therapies. This review will outline the three therapeutic strategies scientists have established and will summarize the most noteworthy clinical trials for each of these strategies.