While Alzheimer disease (AD) is a complex disorder with a strong heritable component, Eric van Exel, from VU University Medical Center (The Netherlands), and colleagues investigated the causal link between amyloid pathology, vascular factors, and inflammation and the onset of AD.  The team studied 206 children of 92 families with a parental history of late-onset AD and 200 offspring of 97 families without a parental history of AD.  Approximately 40% of middle-aged offspring who had a parent with AD had elevated blood pressure, compared with 29% of those without a parental history of the disorder. In addition, these offspring also had a lower brachial index (1.27 versus 1.31), reflecting a higher atherosclerotic burden.  Further, the team found that the production capacity of pro-inflammatory cytokines in offspring with a parental history of AD was also different, with higher levels of interleukin 1beta, IL-1beta-to--IL-1ra ratio, tumor necrosis factor alpha, and interferon gamma, with all of these positive associations being independent of APOE e4 genotype. The researchers conclude that: “Hypertension and the expression of an innate pro-inflammatory cytokine profile in middle age are early risk factors of AD in old age.  For the offspring of affected families, it provides clues for screening and preventive strategies, of which blood pressure control can be implemented directly.”