Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins.
Late-onset sporadic Alzheimer's disease is a heterogeneous disorder. In elderly patients, increasing evidence suggests a link between this neurodegenerative disease, and vascular risk factors and atherosclerosis. The nature of this link remains speculative. Some investigators have suggested that the disease arises as a secondary event related to atherosclerosis of extracranial or intracranial vessels. A toxic effect of vascular factors on the microvasculature of susceptible brain regions has also been argued. An alternative explanation is that atherosclerosis and Alzheimer's disease are independent but convergent disease processes. This hypothesis is lent support by observations of shared epidemiology, pathophysiological elements, and response to treatment in both disorders. It provides a potential framework for an improved understanding of the pathogenesis of Alzheimer's disease, especially in elderly patients with vascular risk factors, and offers some promise toward the search for preventive and therapeutic treatments.
Casserly
Ivan
I
Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Topol
Eric
E
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D001241:Aspirin / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood* / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D007213:Indomethacin / Q000627:therapeutic use; D002537:Intracranial Arteriosclerosis / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D020293:Vasculitis, Central Nervous System / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D001241:Aspirin; D007213:Indomethacin