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Circle of Willis atherosclerosis: association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles.

Abstract

The role of intracranial atherosclerosis in Alzheimer's disease (AD) has been a subject of debate since the first decade of the last century. The initial "vascular hypothesis" of AD was rejected after a series of mid-twentieth century gross anatomical postmortem studies that showed an inconstant relationship between intracranial atherosclerosis and senile dementia. These early studies did not utilize statistical methods, however, and the investigators did not appear to consider the possibility that intracranial atherosclerosis might have a probabilistic, rather than an absolute, effect on AD risk. Recent studies by three independent groups have found a significant statistical association between postmortem measures of circle of Willis atherosclerosis and AD. The present study was undertaken to further address the validity of this association in a large autopsy series, including cases diagnosed neuropathologically with vascular dementia (VaD) and non-AD dementias. Postmortem gross anatomical grading of circle of Willis atherosclerosis was performed in 397 subjects classified by neuropathological diagnosis, including 92 non-demented elderly controls, 215 with AD, 30 with VaD and 60 with non-AD dementias. Circle of Willis atherosclerosis was more severe in subjects with AD and VaD than in control subjects, while it was equivalent between control subjects and subjects with non-AD dementias. Increasing atherosclerotic grade increased the odds ratios (OR) for the diagnoses of both AD and VaD and also increased the ORs for both increased neuritic plaque density and higher Braak neurofibrillary tangle stage. The significance of these associations was retained after consideration of the effects of age, gender and the apolipoprotein E-epsilon4 allele. The results suggest that the statistical association between intracranial atherosclerosis and AD is not an artifact of diagnostic misclassification or of unequal distribution of the apolipoprotein E-epsilon4 allele.

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  • Authors+Show Affiliations

    ,

    W.H. Civin Laboratory for Neuropathology, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA. thomas.beach@sunhealth.org

    , , , , , , , , , ,

    Source

    Acta neuropathologica 113:1 2007 Jan pg 13-21

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Circle of Willis
    Female
    Humans
    Intracranial Arteriosclerosis
    Male
    Neurofibrillary Tangles
    Plaque, Amyloid
    Retrospective Studies
    Severity of Illness Index

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17021755

    Citation

    Beach, Thomas G., et al. "Circle of Willis Atherosclerosis: Association With Alzheimer's Disease, Neuritic Plaques and Neurofibrillary Tangles." Acta Neuropathologica, vol. 113, no. 1, 2007, pp. 13-21.
    Beach TG, Wilson JR, Sue LI, et al. Circle of Willis atherosclerosis: association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles. Acta Neuropathol. 2007;113(1):13-21.
    Beach, T. G., Wilson, J. R., Sue, L. I., Newell, A., Poston, M., Cisneros, R., ... Roher, A. E. (2007). Circle of Willis atherosclerosis: association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles. Acta Neuropathologica, 113(1), pp. 13-21.
    Beach TG, et al. Circle of Willis Atherosclerosis: Association With Alzheimer's Disease, Neuritic Plaques and Neurofibrillary Tangles. Acta Neuropathol. 2007;113(1):13-21. PubMed PMID: 17021755.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Circle of Willis atherosclerosis: association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles. AU - Beach,Thomas G, AU - Wilson,Jeffrey R, AU - Sue,Lucia I, AU - Newell,Amanda, AU - Poston,Marissa, AU - Cisneros,Raquel, AU - Pandya,Yoga, AU - Esh,Chera, AU - Connor,Donald J, AU - Sabbagh,Marwan, AU - Walker,Douglas G, AU - Roher,Alex E, Y1 - 2006/09/20/ PY - 2005/12/05/received PY - 2006/08/22/accepted PY - 2006/08/21/revised PY - 2006/10/6/pubmed PY - 2007/10/30/medline PY - 2006/10/6/entrez SP - 13 EP - 21 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 113 IS - 1 N2 - The role of intracranial atherosclerosis in Alzheimer's disease (AD) has been a subject of debate since the first decade of the last century. The initial "vascular hypothesis" of AD was rejected after a series of mid-twentieth century gross anatomical postmortem studies that showed an inconstant relationship between intracranial atherosclerosis and senile dementia. These early studies did not utilize statistical methods, however, and the investigators did not appear to consider the possibility that intracranial atherosclerosis might have a probabilistic, rather than an absolute, effect on AD risk. Recent studies by three independent groups have found a significant statistical association between postmortem measures of circle of Willis atherosclerosis and AD. The present study was undertaken to further address the validity of this association in a large autopsy series, including cases diagnosed neuropathologically with vascular dementia (VaD) and non-AD dementias. Postmortem gross anatomical grading of circle of Willis atherosclerosis was performed in 397 subjects classified by neuropathological diagnosis, including 92 non-demented elderly controls, 215 with AD, 30 with VaD and 60 with non-AD dementias. Circle of Willis atherosclerosis was more severe in subjects with AD and VaD than in control subjects, while it was equivalent between control subjects and subjects with non-AD dementias. Increasing atherosclerotic grade increased the odds ratios (OR) for the diagnoses of both AD and VaD and also increased the ORs for both increased neuritic plaque density and higher Braak neurofibrillary tangle stage. The significance of these associations was retained after consideration of the effects of age, gender and the apolipoprotein E-epsilon4 allele. The results suggest that the statistical association between intracranial atherosclerosis and AD is not an artifact of diagnostic misclassification or of unequal distribution of the apolipoprotein E-epsilon4 allele. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/17021755/Circle_of_Willis_atherosclerosis:_association_with_Alzheimer's_disease_neuritic_plaques_and_neurofibrillary_tangles_ L2 - https://dx.doi.org/10.1007/s00401-006-0136-y DB - PRIME DP - Unbound Medicine ER -