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

Abstract

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.

• Authors: Kristel Sleegers, Tom den Heijer, Ewoud J van Dijk, Albert Hofman, Aida M Bertoli-Avella, Peter J Koudstaal, Monique M B Breteler, Cornelia M van Duijn
• Journal: Neurobiology of aging (Neurobiol Aging) 2005 Aug-Sep Vol. 26 Issue 8 Pg. 1153-9 ISSN: 0197-4580 [Print] United States
• PMID: 15917098 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptidyl-Dipeptidase A

Topics

• Aged
• Alzheimer Disease (enzymology, genetics, pathology)
• Amygdala (pathology)
• Atrophy (enzymology, genetics, pathology)
• Cerebrovascular Disorders (enzymology, genetics, pathology)
• Cohort Studies
• DNA Mutational Analysis
• Female
• Genetic Predisposition to Disease (genetics)
• Genetic Testing
• Genotype
• Hippocampus (pathology)
• Homozygote
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Nerve Fibers, Myelinated (pathology)
• Netherlands
• Peptidyl-Dipeptidase A (genetics)
• Polymorphism, Genetic (genetics)
• Sex Factors