Sex and Life Experience Converge on Hippocampal Transcriptomic Responses in a Locus Coeruleus Pretangle Tau Model

Locus coeruleus (LC) neurons are among the earliest sites to develop pretangle tau pathology in humans. However, how life experiences interact with early LC tau pathology to influence Alzheimer’s disease (AD) initiation and progression, and whether these effects differ between males and females, remains poorly understood. Using a rat model that recapitulates the human origin of pretangle tau by selectively expressing pseudophosphorylated tau in LC noradrenergic neurons of TH-Cre rats, we investigated how early- and late-life stress and environmental enrichment shape hippocampal transcriptomic responses, with the goal of identifying the earliest molecular events underlying AD pathogenesis.