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

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Abstract

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.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by grants AG079336, AG057842, P20GM104357, and HL138685 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA

    **ng Fang, Chengyun Tang, Huawei Zhang, Jane J. Border, Yedan Liu, Richard J. Roman & Fan Fan

  2. Department of Physiology, Medical College of Georgia, Augusta University, 1462 Laney Walker Blvd, Augusta, GA, 30912, USA

    Chengyun Tang & Fan Fan

  3. Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA

    Seung Min Shin & Hongwei Yu

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  1. **ng Fang
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Contributions

XF and FF conceived and designed research. XF, HZ, JB, YL, SMS, and YL performed experiments; XF, HZ, CT, JB, YL, and FF analyzed data. XF, CT, RJR, and FF interpreted results of experiments. XF, CT, and FF prepared figures. XF and FF drafted the manuscript. CT, SMS, HY, RJR, and FF edited and revised manuscript. All authors read and approved the final version of the manuscript.

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Correspondence to Fan Fan.

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Fang, X., Tang, C., Zhang, H. et al. Longitudinal characterization of cerebral hemodynamics in the TgF344-AD rat model of Alzheimer’s disease. GeroScience 45, 1471–1490 (2023). https://doi.org/10.1007/s11357-023-00773-x

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