Figure 1

Diagram of hypothesis. In response to a persistent or intermittent stimulus, such as cerebral hypoxia, brain endothelial cells become activated. Activated endothelial cells are highly synthetic and release a host of factors that can affect the activation of nearby cells. Despite the continued presence of the stimulus, no new vessel growth occurs. Because no new vessels are formed there are no feedback signals to shut off vascular activation endothelial cells, as occurs in physiologic angiogenesis. In AD reversible endothelial activation becomes irreversible endothelial dysfunction. The vascular products of a permanently dysfunctional endothelium could cause neuronal injury/death directly or via activation of microglia and/or astrocytes. (blue line) = feedback inhibition, (yellow lighting bolt) = Endothelial cell products