Interaction between amyloid-β and tau protein:Insights into AD pathological mechanism from the perspective of extracellular tau clearance

Risa Nishiyama, Kaoru Yamada

Department of Neuropathology, Graduate School of Medicine, The University of Tokyo

During the progression of Alzheimer's disease （AD）, the accumulation of extracellular amyloid-β （Aβ） exacerbates intraneuronal tau aggregation, ultimately leading to neurodegeneration.　However, the precise underlying mechanism connecting these two abnormal protein aggregations remains elusive.　Previous studies have primarily focused on the effects of Aβ accumulation on intraneuronal tau phosphorylation, subcellular localization, or seed-dependent aggregation.　In addition to these findings, we have explored the impact of Aβ on tau dynamics and found the dysfunction of the glymphatic clearance of extracellular tau in the presence of Aβ accumulation.　In this review, we will provide an overview of the molecular mechanisms linking Aβ and tau and also introduce our research findings on the tau clearance mechanism mediated by the glymphatic system and the impact of Aβ accumulation.　The discussion will encompass the remaining questions and future research directions.

Address correspondence to Dr. Kaoru Yamada, Department of Neuropathology, Graduate School of Medicine, The University of Tokyo （Univ Tokyo, Med 3rd Bldg 7th Floor, Rm S701, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan）