The strongest known risk factors for late-onset Alzheimer disease (LOAD) remain a positive family history and the APOE ε4 allele. van Exel and colleagues used these known risk factors to identify high- and low-risk samples of middle-aged persons in whom they compared levels of inflammatory and vascular risk factors. They observed that, compared with controls, middle-aged offspring of families with a parental history of LOAD had higher blood pressures, lower ankle-brachial indices (measure of peripheral atherosclerosis), and increased production of proinflammatory cytokines in lipopolysaccharide-stimulated whole blood samples, associations that were independent of APOE genotype. This study adds to the growing body of evidence linking inflammatory mechanisms to Alzheimer disease risk and, especially when considered in light of the recently described association of genetic variation in the complement receptor 1 (CR1) gene with LOAD, suggests that inflammatory biomarkers (whether causal or incidental) could be measured and perhaps used to risk-stratify middle-aged persons for early preventive and therapeutic interventions.
