Temporal and region-specific tau hyperphosphorylation in the medulla and forebrain coincides with development of functional changes in male obese Zucker rats

Male obese Zucker rats (OZRs) lack functional leptin receptors and develop metabolic syndrome (MetS). At 16–19 wk, OZRs are insulin resistant, with increased ptau in dorsal medulla and impaired autonomic regulation of AP. At 28–29 wk OZRs develop increased ptau in hippocampus with deficits in spatial learning and memory. Juvenile OZRs lack elevated ptau and these deficits, demonstrating that leptin is not essential for normal function. Elevated ptau and deficits emerge before the onset of diabetes in insulin-resistant OZRs.