Work

Tau spread plays an etiopathogenic connection between seizures and Alzheimer’s disease

Year: 2026

Type: article

Abstract: Patients with Alzheimer's disease (AD) display heightened seizure susceptibility, in which neuronal hyperactivity during seizures correlates with exacerbated Tau pathology and cognitive impairment. This study integrated public transcriptomic datasets with machine learning approaches, suggesting Tau spread as a key biological association between seizure activity and AD. We validated activity-dependent Tau release under epileptic stimulation using primary neurons and human induced pluripotent stem cells (hiPSC)-derived neuronal models. Further validation in an AAV-based mouse Tau propagation model revealed robust bidirectional interactions: pathological Tau overexpression worsened seizure outcomes, while seizures accelerated Tau propagation across brain regions, inducing neuronal loss and gliosis. This study characterizes the activity-regulated interplay between epileptic activity and AD-associated Tau pathology, offering a potential therapeutic target for AD comorbid with epilepsy.

Source: iScience

DOI: 10.1016/j.isci.2026.117747