Hypertension and evidence of arterial disease and a pro-inflammatory status in middle age contribute to the development of Alzheimer’s disease, say researchers. 4 November 2009Their study showed people aged around 50 years with a parental history of AD had higher systolic and diastolic blood pressures (BPs), lower ankle brachial indices, and greater production of pro-inflammatory cytokines than those with no family history of the disease. Late-onset AD is a complex but heritable polygenic disorder for which the identification of specific genetic risk markers has proved difficult through genome association studies. Using a proven family design study, Eric van Exel (VU University Medical Center, Amsterdam, The Netherlands) and team sought to identify and quantify early risk factors that contribute to AD. They recruited 206 offspring (mean age 49 years) of 92 families with a parental history of late-onset AD, and 200 offspring (mean age 52 years) of 97 families without such parental history, and compared various factors known to be associated with an increased risk for AD between the groups. “In such a family design, the offspring under study are enriched for risk factors of AD but do not yet have the disease,” the researchers explain in the Archives of General Psychiatry. “Differences between offspring dependent on their ancestry therefore lend an argument for causality.” Results showed that more offspring with parental history of AD carried the apolipoprotein E gene (APOE) ε4 variant, a known genetic risk factor for AD, than did those without a parental history of the disease (47% vs 21%, p<0.001). p="0.006)">139 mmHg or diastolic BP >89 mmHg; 40% vs 29%, p=0.02). Brachial ankle indices were on average lower in offspring with a parental history of AD (1.27 vs 1.31, p=0.005), reflecting a higher atherosclerotic burden, but lipid, glucose, and homocysteine levels did not differ significantly between groups. The researchers also found that individuals with a parental history of AD had a greater production capacity for pro-inflammatory cytokines than those without such history, with significantly higher levels of interleukin (IL)-1β, IL-1β to IL-1ra ratio, tumor necrosis factor α, IL-6, and interferon γ. Further analysis showed these associations remained true after adjusting for caregiver stress, education level, and lifestyle factors, use of anti-inflammatory drugs, and APOE ε4 allele frequency, and that they did not differ between APOE ε4 carriers and noncarriers.