Alzheimer Disease is not associated with polymorphisms in the angiotensinogen and renin genes

Hypertension has been implicated as a riskfactor for Alzheimer disease (AD) anddementia in epidemiological studies ofhumans. It is thus possible that there arecommon genetic determinants for hyperten-sion and AD. Epidemiological, clinical, andexperimental data suggest that the renin-angiotensin-aldosterone system is a criticalregulator of blood pressure. The presence ofanMboI site in an RFLP in the renin geneand the Thr at the Met/Thr polymorphism atcodon 235 (M235T) of the angiotensinogengene have been reported to be associatedwith hypertension. These variants werestudied in autopsy-conÆrmed AD cases andmatched controls from the U.K. While noassociation was detected with the reninpolymorphism, a weak deleterious effectwas observed in cases homozygous for theangiotensinogen Thr allele. However, thisassociation was not observed in a Frenchcohort of clinically diagnosed AD cases andcontrols, suggesting that the initial observa-tion was a type I error. Thus, these poly-morphisms are unlikely to be associatedwith AD risk.