Longitudinal characterization of cerebral hemodynamics in the TgF344-AD rat model of Alzheimer’s disease

Alzheimer's disease (AD) is a global healthcare crisis. The TgF344-AD rat is an AD model exhibiting age-dependent AD pathological hallmarks. We confirmed that AD rats developed cognitive deficits at 6 months without alteration of any other major biophysical parameters. We longitudinally characterized cerebral hemodynamics in AD rats at 3, 4, 6, and 14 months. The myogenic responses of the cerebral arteries and arterioles were impaired at 4 months of age in the AD rats. Consistent with the ex vivo results, the AD rat exhibited poor autoregulation of surface and deep cortical cerebral blood flow 2 months preceding cognitive decline. The dysfunction of cerebral hemodynamics in AD is exacerbated with age associated with reduced cerebral perfusion. Further, abolished cell contractility contributes to cerebral hemodynamics imbalance in AD. This may be attributed to enhanced ROS production, reduced mitochondrial respiration and ATP production, and disrupted actin cytoskeleton in cerebral vascular contractile cells.