Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication




Journal article


Neurobiol Aging

Publication Date





1153 - 1159


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