Failure of DNA double-strand break repair by tau mediates Alzheimer’s disease pathology in vitro

• DOI: 10.1038/s42003-022-03312-0
• Publication Date: 2022-04-13T10:14:25Z
• Authors: Megumi Asada-Utsugi; Kengo Uemura; Takashi Ayaki; Maiko T. Uemura; Sumio Minamiyama; Ryota Hikiami; Toshifumi Morimura; Akemi Shodai; Takatoshi Ueki; Ryosuke Takahashi; Ayae Kinoshita; Makoto Urushitani
• Keywords: Tauopathy; Tau protein

Abstract DNA double-strand break (DSB) is the most severe form of damage and accumulates with age, in which cytoskeletal proteins are polymerized to repair DSB dividing cells. Since tau a microtubule-associated protein, we investigate whether involved pathologies Alzheimer’s disease (AD). First, immunohistochemistry reveals frequent coexistence phosphorylated cortex AD patients. In vitro studies using primary mouse cortical neurons show that non-p-tau perinuclearly together tubulin after induction etoposide, followed by accumulation tau. Moreover, knockdown endogenous exacerbates neurons, suggesting protective role on repair. Interestingly, synergistic exposure microtubule disassembly strikingly augments aberrant p-tau aggregation apoptosis. These data suggest plays pivotal AD-tau pathology failure leads tauopathy.