Tau Repeats Disassemble Amyloid-β Fibrils In Vitro by Interacting with KLVFFA and GGVVIA Domains

The interplay between amyloid beta (Aβ) and tau protein is acknowledged as a crucial factor in the progression of Alzheimer's disease (AD), yet the precise molecular mechanisms underlying their interaction remain elusive. In this study, we explore how the key regions within tau, specifically the repeat domains, modulate Aβ aggregation. Through microscale thermophoresis and peptide mapping assays, we identified that tau repeats containing the amyloid motifs VQIINK and VQIVYK directly interact with Aβ(1-42) and Aβ(1-40), targeting the hydrophobic regions of Aβ. Tau repeats were found to inhibit Aβ fibril formation and promote the dissociation of preformed fibrils in vitro. Notably, while disassembling Aβ(1-42) fibrils, tau repeats concurrently stabilized oligomeric forms. These findings provide valuable insights into the complex mechanisms by which tau influences the Aβ pathology, with potential implications for AD progression.