Hyperactive neuronal networks enhance tau spread in an Alzheimer's disease mouse model.

ABSTRACT: Pathological tau spreads via neuronal connections in Alzheimer's disease (AD). Given the high incidence and deleterious consequences of epileptiform activity in AD, we hypothesized that neuronal hyperactivity and seizures exacerbate tau spread. To examine the impacts of brain-wide network and population hyperactivity on tau spread, we created a novel mouse model involving the cross of targeted recombination in active populations (TRAP) and the 5 times familial AD mice (5X-TRAP) that allows for the permanent labelling of seizure-activated neurons. To explore the effects of seizures on tau spread, we injected these mice with human AD brain-derived tau to induce pathological tau spread, and induced seizures with pentylenetetrazol (PTZ) kindling. Brain mapping revealed that seizures increased

SUBMITTER: Barbour AJ 

PROVIDER: S-EPMC11642807 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature