title: 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.affiliation: Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.forename: Tom
authors.initials: T
authors.lastname: den Heijer
authors.forename: Ewoud J
authors.initials: EJ
authors.lastname: van Dijk
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Aida M
authors.initials: AM
authors.lastname: Bertoli-Avella
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koudstaal
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000679:Amygdala / Q000473:pathology*; D001284:Atrophy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009426:Netherlands; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012737:Sex Factors
chemical_list: D007703:Peptidyl-Dipeptidase A