Brain Homogenates from Alzheimer's Patients Impact Vascular Function

Alzheimer's disease (AD) is characterized by a state of reduced cerebral blood flow, which may partly be secondary to cerebral artery vascular dysfunction. Recent studies have shown that systemic vascular dysfunction may precede Alzheimer's disease. We hypothesize that biochemical changes associated with AD progression can impact vascular function. Homogenates were prepared from temporal lobe samples from patients with or without tauopathies and were categorized into three groups: homogenates with amyloid Tau protein, homogenates with high concentrations of Tau protein but little amyloids, and control. The chronic effects of brain homogenates on vascular function was characterized using isolated wild‐type rat aorta segments incubated with homogenates (0.1% or 1%) for 24 hours. Rat aortas were isometrically mounted and the vascular function was assessed by examining contractile responses to KCl and phenylephrine, and relaxation responses to methacholine and sodium nitroprusside. The acute effect of homogenates on vascular function was measured using wild‐type rat aorta segments after maximal relaxation by methacholine. Preliminary data from chronic studies suggests that, amyloid group patient tissues are less sensitive to methacholine‐dependent relaxation compared to tissue from Tau and control groups(One‐way ANOVA; p<0.05). Preliminary data from acute studies suggests that tissue from the tau group results in more severe contractile effects on maximally relaxed aortas compared to amyloid and control groups. These results are significant because they suggest that biochemical changes associated with AD can impact vascular function. Therefore, these studies suggest that there is an association between AD and vascular dysfunction. Support or Funding Information Supported by grant AG051633 from NIA./NIH and SIRE to XZ