Fifty million people worldwide are estimated to have dementia, with Alzheimer’s disease—accounting for over 70%—being the representative neurodegenerative brain disorder.
A Korean research team has, for the first time in the world, identified at the molecular level that tau and amyloid-β, the two key pathological proteins of Alzheimer’s disease, directly communicate to regulate toxicity. This achievement is expected to provide new insights into the pathophysiology of Alzheimer’s disease, as well as important clues for discovering biomarkers for early diagnosis and developing therapeutics for neurodegenerative brain disorders.
KAIST announced that Mi Hee Lim’s research team in the Department of Chemistry, in collaboration with Young-Ho Lee’s team from the Division of Advanced Biomedical Research at the Korea Basic Science Institute under the National Research Council of Science & Technology, together with Yun Kyung Kim and Sung Su Lim from the Brain Science Institute at the Korea Institute of Science and Technology, has elucidated at the molecular level that the microtubule-binding domain of tau—one of the major pathological proteins of Alzheimer’s disease—directly interacts with amyloid-β (tau–amyloid-β communication), alters its aggregation pathway, and alleviates cellular toxicity.
Pathologically, Alzheimer’s disease is characterized by the accumulation of“neurofibrillary tangles” formed by aggregates of tau, a protein responsible for transporting nutrients and signaling molecules within neurons, and “amyloid plaques (senile plaques)” formed by clusters of amyloid-β fragments—abnormally cleaved from amyloid precursor protein, which is involved in brain development, intercellular signaling, and neuronal recovery—that aggregate in and around neuronal membranes in the brain.
Although tau and amyloid-β form pathological structures in spatially separated locations, it has been suggested that they may coexist inside and outside of cells and potentially interact. However, the molecular-level understanding of how their direct interaction affects the onset and progression of the disease has not been clearly revealed until now.
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