Int J Biol Sci 2021; 17(9):2181-2192. doi:10.7150/ijbs.57078


Interaction between Aβ and Tau in the Pathogenesis of Alzheimer's Disease

Huiqin Zhang1, Wei Wei1, Ming Zhao2, Lina Ma1, Xuefan Jiang2, Hui Pei1, Yu Cao1✉, Hao Li1✉

1. Institute of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
2. Beijing University of Chinese Medicine, Beijing 100029, China.

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Zhang H, Wei W, Zhao M, Ma L, Jiang X, Pei H, Cao Y, Li H. Interaction between Aβ and Tau in the Pathogenesis of Alzheimer's Disease. Int J Biol Sci 2021; 17(9):2181-2192. doi:10.7150/ijbs.57078. Available from

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Extracellular neuritic plaques composed of amyloid‑β (Aβ) protein and intracellular neurofibrillary tangles containing phosphorylated tau protein are the two hallmark proteins of Alzheimer's disease (AD), and the separate neurotoxicity of these proteins in AD has been extensively studied. However, interventions that target Aβ or tau individually have not yielded substantial breakthroughs. The interest in the interactions between Aβ and tau in AD is increasing, but related drug investigations are in their infancy. This review discusses how Aβ accelerates tau phosphorylation and the possible mechanisms and pathways by which tau mediates Aβ toxicity. This review also describes the possible synergistic effects between Aβ and tau on microglial cells and astrocytes. Studies suggest that the coexistence of Aβ plaques and phosphorylated tau is related to the mechanism by which Aβ facilitates the propagation of tau aggregation in neuritic plaques. The interactions between Aβ and tau mediate cognitive dysfunction in patients with AD. In summary, this review summarizes recent data on the interplay between Aβ and tau to promote a better understanding of the roles of these proteins in the pathological process of AD and provide new insights into interventions against AD.

Keywords: Alzheimer's disease, amyloid-β, tau, interaction, phosphorylation