Excitatory amino acid transporter 2 associates with phosphorylated tau and is localized in neurofibrillary tangles of tauopathic brains

AbstractPhosphorylated tau (p-tau) is the principal component of neurofibrillary tangles, a pathological hallmark, and likely plays a neurotoxic role in tauopathies including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). We subjected brains from autopsy cases of AD, PSP, and CBD to a variety of immunohistochemical, immunoblotting, and pull-down assays. In this study, we show that excitatory amino acid transporter 2 (EAAT2) preferentially interacted with phosphorylated tau and was localized in neurofibrillary tangles in the brains of such patients. These results strongly indicate that EAAT2 acts in tauopathy-related neurodegeneration, and abnormalities in glutamate transport play an important role in the pathogenesis of tauopathies.Structured summaryMINT-7148349, MINT-7148361:TAU (uniprotkb:P10636) physically interacts (MI:0914) with EAAT2 (uniprotkb:P43004) by pull-down (MI:0096)MINT-7148372, MINT-7148384:TAU (uniprotkb:P10636) physically interacts (MI:0914) with EAAT2 (uniprotkb:P43004) by anti bait coimmunoprecipitation (MI:0006