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A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer's disease.

Abstract

The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin loss (ML) was investigated in four regions of the cerebral cortex in an autopsy-confirmed series of 93 patients with Alzheimer's disease (AD). The possible influence of APO E epsilon4 allele acting in concert with ACE D allele was assessed. The extent of ML did not differ between D/D, I/D and I/I genotype groups when data from all four brain regions were combined. However, separate analysis showed that the frontal and temporal cortex tended to be affected more severely by ML in patients with D/D genotype compared to those with I/D and I/I genotypes. Stratification according to APO E epsilon4 allele revealed a greater overall ML in patients bearing at least one copy of ACE D allele and one APO E epsilon4 allele, especially in individuals homozygous for both. The APO E epsilon4 allele may therefore act synergistically in patients with AD (and other subjects) bearing ACE D/D genotype to increase the risk of ML, perhaps through transient ischaemic episodes consequent upon poor cardiac output associated with coronary atherosclerosis in patients with the APO E epsilon4 allele.

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  • Authors+Show Affiliations

    ,

    Clinical Neuroscience Research Group, Department of Medicine, University of Manchester, Manchester, M13 9PT, UK.

    , , , , , , , ,

    Source

    Neuroscience letters 354:2 2004 Jan 09 pg 103-6

    MeSH

    Adult
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Apolipoprotein E4
    Apolipoproteins E
    Cerebral Cortex
    Coronary Artery Disease
    Female
    Gene Frequency
    Genetic Predisposition to Disease
    Genotype
    Humans
    Ischemic Attack, Transient
    Male
    Middle Aged
    Nerve Degeneration
    Nerve Fibers, Myelinated
    Peptidyl-Dipeptidase A
    Polymorphism, Genetic

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    14698449

    Citation

    Tian, J, et al. "A Polymorphism in the Angiotensin 1-converting Enzyme Gene Is Associated With Damage to Cerebral Cortical White Matter in Alzheimer's Disease." Neuroscience Letters, vol. 354, no. 2, 2004, pp. 103-6.
    Tian J, Shi J, Bailey K, et al. A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer's disease. Neurosci Lett. 2004;354(2):103-6.
    Tian, J., Shi, J., Bailey, K., Harris, J. M., Pritchard, A., Lambert, J. C., ... Mann, D. M. (2004). A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer's disease. Neuroscience Letters, 354(2), pp. 103-6.
    Tian J, et al. A Polymorphism in the Angiotensin 1-converting Enzyme Gene Is Associated With Damage to Cerebral Cortical White Matter in Alzheimer's Disease. Neurosci Lett. 2004 Jan 9;354(2):103-6. PubMed PMID: 14698449.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer's disease. AU - Tian,J, AU - Shi,J, AU - Bailey,K, AU - Harris,J M, AU - Pritchard,A, AU - Lambert,J-C, AU - Chartier-Harlin,M-C, AU - Pickering-Brown,S M, AU - Lendon,C L, AU - Mann,D M A, PY - 2003/12/31/pubmed PY - 2004/3/12/medline PY - 2003/12/31/entrez SP - 103 EP - 6 JF - Neuroscience letters JO - Neurosci. Lett. VL - 354 IS - 2 N2 - The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin loss (ML) was investigated in four regions of the cerebral cortex in an autopsy-confirmed series of 93 patients with Alzheimer's disease (AD). The possible influence of APO E epsilon4 allele acting in concert with ACE D allele was assessed. The extent of ML did not differ between D/D, I/D and I/I genotype groups when data from all four brain regions were combined. However, separate analysis showed that the frontal and temporal cortex tended to be affected more severely by ML in patients with D/D genotype compared to those with I/D and I/I genotypes. Stratification according to APO E epsilon4 allele revealed a greater overall ML in patients bearing at least one copy of ACE D allele and one APO E epsilon4 allele, especially in individuals homozygous for both. The APO E epsilon4 allele may therefore act synergistically in patients with AD (and other subjects) bearing ACE D/D genotype to increase the risk of ML, perhaps through transient ischaemic episodes consequent upon poor cardiac output associated with coronary atherosclerosis in patients with the APO E epsilon4 allele. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/14698449/A_polymorphism_in_the_angiotensin_1_converting_enzyme_gene_is_associated_with_damage_to_cerebral_cortical_white_matter_in_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304394003011789 DB - PRIME DP - Unbound Medicine ER -