Developmental origins of aging in brain and blood vessels: an overview.
Emerging evidence suggests a remarkable convergence of inflammatory mechanisms in the etiology of cardiovascular disease and Alzheimer disease. A broad set of NSAIDs and statins used to reduce the risk of vascular occlusion and to slow atherogensis may also be protective for Alzheimer disease. Elevated blood levels of C-reactive protein are risk factors for cardiovascular disease and possibly for Alzheimer disease. Monocyte-lineage cells are also fundamental to both conditions: in blood vessels, macrophages are important to atherogenesis for the accumulation of lipids (foam cells), whereas brain microglia show activation during aging and direct involvement in amyloid metabolism in the senile plaque. Genetic influences are recognized through the apoE4 allele, which is associated with hypercholesterolemia and is a risk factor in vascular events and Alzheimer disease, and is recognized for its proinflammatory profile. ApoE4 also accelerates Alzheimer disease pathogenesis in Down's syndrome and many other chronic neurodegenerative conditions, as is well-supported by animal models. Inflammatory changes are present at the earliest stages of vascular disease and Down's syndrome in human fetuses, and are also prominent early in Alzheimer disease. These findings give a basis for considering inflammatory processes early in life which can lead to fully fired pathogenesis of cardiovascular disease and possibly for Alzheimer disease.
Finch
Caleb E
CE
Department of Biological Sciences, Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089-0191, USA. cefinch@usc.edu
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000503:physiopathology* / Q000517:prevention & control; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000502:physiology*; D001161:Arteriosclerosis / Q000188:drug therapy / Q000503:physiopathology*; D001808:Blood Vessels / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D058225:Plaque, Amyloid / Q000502:physiology; D014652:Vascular Diseases / Q000188:drug therapy / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D004791:Enzyme Inhibitors