• angiotensin I converting enzyme
• genetics
• Alzheimer’s disease

Early studies suggested that angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE) gene polymorphism is associated with an increased risk of coronary artery disease and, more recently, with sporadic late onset Alzheimer’s disease.¹ Studies conducted in northern European populations have considered the ACE*I allele to be a risk factor for various types of cognitive decline.^1,2 One such study in a French population found an association between the ACE*D allele and dementia,³ while other studies in southern European populations found either a slight but significantly increased frequency of ACE*I in Alzheimer’s disease patients⁴ or did not detect any effect of ACE polymorphism.⁵

Our group recently reported the novel finding that apolipoprotein E (APOE) ε4 allele shows a geographical trend, decreasing in frequency from northern to southern Europe.⁶ We hypothesised that the variability in the strength of evidence for an association between ACE polymorphism and Alzheimer’s disease was related to similar geographical variations in ACE*I frequency. We investigated whether there was evidence in southern Italy of an association between the ACE polymorphism and increased risk of Alzheimer’s disease. Secondly, we compared our results with the findings from published studies on other European populations.^1,2,4

Between June 1998 and October 2001, we consecutively examined in our centre 141 patients with Alzheimer’s disease (51 men, 90 women; mean (SD) age at onset, 71 (8.5) years), and 268 unrelated caregivers, spouses, friends, neighbours, or volunteers (118 men, 150 women; mean age …