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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.

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  • Authors+Show Affiliations

    ,

    Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.

    , , , , , ,

    Source

    Neurobiology of aging 26:8 pg 1153-9

    MeSH

    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

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15917098

    Citation

    Sleegers, Kristel, et al. "ACE Gene Is Associated With Alzheimer's Disease and Atrophy of Hippocampus and Amygdala." Neurobiology of Aging, vol. 26, no. 8, 2005, pp. 1153-9.
    Sleegers K, den Heijer T, van Dijk EJ, et al. ACE gene is associated with Alzheimer's disease and atrophy of hippocampus and amygdala. Neurobiol Aging. 2005;26(8):1153-9.
    Sleegers, K., den Heijer, T., van Dijk, E. J., Hofman, A., Bertoli-Avella, A. M., Koudstaal, P. J., ... van Duijn, C. M. (2005). ACE gene is associated with Alzheimer's disease and atrophy of hippocampus and amygdala. Neurobiology of Aging, 26(8), pp. 1153-9.
    Sleegers K, et al. ACE Gene Is Associated With Alzheimer's Disease and Atrophy of Hippocampus and Amygdala. Neurobiol Aging. 2005;26(8):1153-9. PubMed PMID: 15917098.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - ACE gene is associated with Alzheimer's disease and atrophy of hippocampus and amygdala. AU - Sleegers,Kristel, AU - den Heijer,Tom, AU - van Dijk,Ewoud J, AU - Hofman,Albert, AU - Bertoli-Avella,Aida M, AU - Koudstaal,Peter J, AU - Breteler,Monique M B, AU - van Duijn,Cornelia M, Y1 - 2004/11/24/ PY - 2004/06/28/received PY - 2004/09/27/revised PY - 2004/09/28/accepted PY - 2005/5/27/pubmed PY - 2005/8/19/medline PY - 2005/5/27/entrez SP - 1153 EP - 9 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 26 IS - 8 N2 - 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. SN - 0197-4580 UR - https://www.unboundmedicine.com/medline/citation/15917098/ACE_gene_is_associated_with_Alzheimer's_disease_and_atrophy_of_hippocampus_and_amygdala_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(04)00315-X DB - PRIME DP - Unbound Medicine ER -