O R I G I N A L R E S E A R C H Lack of association between angiotensin- conver ting enzyme and dementia of the Alzheimer’s type in an elderly Arab population in Wadi Ara, Israel Abdalla Bowirrat1,2,3 Jing Cui4 Kristin Waraska5 Robert P Friedland10 Marlene Oscar-Berman2,3,6 Lindsay A Farrer1,6,7,8,9 Amos Korczyn11 Clinton T Baldwin1,5,7 1Genetic Program, 2Department of Anatomy and Neurobiology, 3Division of Psychiatry, 4Hypertension Section, 5Center for Human Genetics, 6Department of Neurology, 7Department of Genetics and Genomics, Boston University School of Medicine, Boston, MA, USA; 8Department of Epidemiology, 9Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; 10Department of Neurology, Case Western Reserve University, Cleveland, OH, USA; 11Department of Neurology, Tel Aviv University, Tel Aviv, Israel Correspondence: Abdalla Bowirrat Department of Anatomy and Neurobiology, Laboratory of Neuropsychology, Boston University School of Medicine, 715 Albany Street, L-815 Boston, MA 02118, USA Tel +1 617 638 4807 Fax +1 617 638 4806 Email bowirrat@bu.edu Abstract: The angiotensin-converting enzyme (ACE), a protease involved in blood pressure regulation, has been implicated as an important candidate gene for Alzheimer’s disease (AD). This study investigated whether the ACE gene insertion–deletion (ID) polymorphism is associated with risk of developing dementia of Alzheimer’s type (DAT) in an Arab–Israeli community, a unique genetic isolate where there is a high prevalence of DAT. In contrast to several other studies, we found no evidence of an association between this polymorphism and either DAT or age-related cognitive decline (ARCD). Keywords: angiotensin-converting enzyme, dementia of the Alzheimer’s type, age-related cognitive decline, insertion–deletion polymorphism, Arab population Introduction Alzheimer’s disease (AD) is a catastrophic affliction of the middle and later years of life. Clinically, it is marked by an irreversible decline in mental abilities, including progressive loss of memory, confusion, and dementia, and culminates in childlike helplessness. In the United States, the incidence of AD is exponentially increasing and is projected to affect 8.64 million people by the year 2047 (Grossberg 2003). Median survival times range from 8.3 years for persons diagnosed at age 65, to 3.4 years for persons diagnosed at age 90 (Brookmeyer et al 2002). Angiotensin-converting enzyme (ACE) catalyzes the conversion of angiotensin I into a physiologically active peptide, angiotensin II. This reaction is an important process in blood pressure regulation. In addition to this well known physiologic role, ACE is able to cleave other proteins, including bradykinin and substance P, and has been shown to inhibit and cleave amyloid β-peptide (Aβ) aggregation and amyloid plaque formation in vitro (Hu et al 2001). ACE may contribute to the pathogenesis of AD. To test the hypothesis of association between ACE and DAT, we evaluated an insertion–deletion (ID) polymorphism in the ACE gene as a potential risk factor for dementia of the Alzheimer’s type (DAT) in an Arab community in Wadi Ara, Israel. The population comprised 853 persons over the age of 65 (Bowirrat et al 2001; Bowirrat, Friedland, Farrer, et al 2002). Family studies revealed that more than one- third of DAT cases are members of one extended family. We hypothesized that DAT in Wadi Ara may be due to a founder effect enhanced by consanguinity; thus, a specific disease susceptibility allele may be overrepresented in cognitively impaired subjects compared with cognitively healthy residents. Our results suggest that the Neuropsychiatric Disease and Treatment 2005:1(1) 73 –76 © 2005 Dove Medical Press Limited. All rights reserved 73