Angiogenic Mediators and the Pathogenesis of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a progressive, neurodegenerative disease that affects more than 5 million people in the United States. At present, no disease-modifying drugs are available; new therapeutic approaches are desperately needed. Considerable evidence links vascular dysfunction, vascular risk factors, and the pathogenesis of AD. Data are emerging to support the idea that factors and processes characteristic of angiogenesis are found in AD brain. Genome-wide expression profiling in the AD brain has identified a marked upregulation of genes that promote angiogenesis. Epidemiological studies suggest that some drugs purported to have beneficial effects in AD inhibit angiogenesis. Hypoxia is known to stimulate angiogenesis as well as contribute to the clinical and pathological manifestations of AD. Angiogenesis inhibitors may represent an important and unexplored class of therapeutic drugs for AD. The cerebral microcirculation could be a new target for therapeutic intervention in AD. Identification of “vascular activation” as a target in AD would stimulate translational investigations in this newly defined area and may lead to novel therapeutic approaches for the treatment of this devastating disease.