ACE gene is associated with Alzheimer's disease and atrophy of hippocampus and amygdala

• Published in: Neurobiology of aging 2005-08, Vol.26 (8), p.1153-1159
• Main Authors: Sleegers, Kristel, den Heijer, Tom, van Dijk, Ewoud J., Hofman, Albert, Bertoli-Avella, Aida M., Koudstaal, Peter J., Breteler, Monique M.B., van Duijn, Cornelia M.
• Format: Article
• Language: English
• Subjects: ACE gene; Aged; Alzheimer Disease - enzymology; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amygdala; Amygdala - pathology; Atrophy - enzymology; Atrophy - genetics; Atrophy - pathology; Biological and medical sciences; Cerebrovascular Disorders - enzymology; Cerebrovascular Disorders - genetics; Cerebrovascular Disorders - pathology; Cohort Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Mutational Analysis; Female; Genetic Predisposition to Disease - genetics; Genetic Testing; Genotype; Hippocampus; Hippocampus - pathology; Homozygote; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Nerve Fibers, Myelinated - pathology; Netherlands; Neurology; Peptidyl-Dipeptidase A - genetics; Polymorphism, Genetic - genetics; Sex Factors; Vascular risk factors; White matter hyperintensities
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2004.09.011

Despite biological support for a role of angiotensin converting enzyme (ACE) in Alzheimer's disease (AD), studies assessing the ACE I/D polymorphism in AD are conflicting. We re-evaluated this association in the Rotterdam Study, a population-based cohort study. The mechanism of association was further explored by adjusting for vascular factors, and by analysing atrophy, white matter lesions and infarcts on MRI in non-demented individuals. Genotypes were available for 6488 participants. During average follow-up of 6 years 250 subjects developed AD. MRI data were available for 494 non-demented participants. Homozygosity for the I-allele conferred a slightly increased risk of AD compared to carrying a D-allele (RR 1.12 (95% CI 0.99–1.25)). This increase was only significant in women, and independent of vascular factors (RR 1.39 (95% CI 1.14–1.69)). Non-demented women with the II genotype had smaller hippocampal and amygdalar volumes. Vascular pathology was not significantly associated with ACE. This suggests a modest but significant increase in risk of AD and early AD pathology in women homozygous for the ACE I-allele independent of vascular factors.