Cerebrovascular capillary density and glycocalyx deficits in the TgF344-AD rat model of Alzheimer’s disease

Introduction: – Cerebral perfusion declines and cerebrovascular regulation worsens with age, potentially contributing to the pathogenesis of Alzheimer’s disease (AD). The role of the endothelial glycocalyx, which regulates multiple microvascular functions related to cerebrovascular dysfunction in AD, remains understudied in clinical and preclinical models of AD. The aim of the present study was to establish the feasibility of assessing cerebrovascular function by assessing both vascular reactivity of resistance arteries and microvascular anatomy in male and female TgF344-AD rats. Methods: – A craniotomy was performed, and intravital microscopy with sidestream dark field imaging was used to assess the exposed subdural microcirculation (Capiscope HCVS, KK Technology) in transgenic (AD) and wild type (WT) rats. Videos were analyzed and variables were quantified automatically with GlycoCheckä Software (GlycoCalyx Research Institute). Subsequently, posterior cerebral arteries were isolated. Myogenic constriction to intraluminal pressure and endothelium-dependent vasodilation to intraluminal flow were evaluated. Endothelium-independent vasodilation to DEA-NONOate, an exogenous nitric oxide (NO) donor, was also evaluated. Results: – In 10-18 mm vessels, perfused boundary region, a measure of glycocalyx function, was higher in AD compared to WT animals (p=0.0433, 2.33 ± 0.22 vs 2.65 ± 0.23 mm), indicating worse functionality. Cerebral capillary density (p=0.0285, 24.3 ± 3.4 vs 33.5 ± 8.1 mm/mm2) and capillary blood volume (p=0.0474, 3.37 ± 0.71 vs 4.76 ± 1.33 103 µm3) were also decreased in AD animals compared to WT. Myogenic constriction and vasodilation to flow were not changed in resistance arteries from AD animals. EC50 analysis of vasodilatory responses to DEA-NONOate revealed increased sensitivity to NO in resistance arteries from AD animals (p=0.0319). Conclusions: – The present study demonstrates deficits in glycocalyx function, reduced capillary density, and increased sensitivity to NO in the cerebrovasculature of AD TgF344-AD rats in comparison to WT littermates. These findings give mechanistic insight into AD-associated cerebrovascular dysfunction. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.