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Updated: Jul 12, 2025

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Tau truncation in the pathogenesis of Alzheimer's disease: a narrative review
Dandan Chu1, Xingyue Yang2, Jing Wang2
1Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.
Abstract:
Alzheimer's disease is characterized by two major neuropathological hallmarks-the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubule-associated protein Tau, especially specific proteolysis, could be a driving force for Alzheimer's disease neurodegeneration. Tau physiologically promotes the assembly and stabilization of microtubules, whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers, resulting in them gaining prion-like characteristics. In addition, Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner. This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments, investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease, and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.
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