Circle of Willis atherosclerosis

Association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles

Thomas G. Beach, Jeffrey Wilson, Lucia I. Sue, Amanda Newell, Marissa Poston, Raquel Cisneros, Yoga Pandya, Chera Esh, Donald J. Connor, Marwan Sabbagh, Douglas G. Walker, Alex E. Roher

Research output: Contribution to journalArticle

161 Citations (Scopus)

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-ε4 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-ε4 allele.

Original languageEnglish (US)
Pages (from-to)13-21
Number of pages9
JournalActa Neuropathologica
Volume113
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Circle of Willis
Neurofibrillary Tangles
Amyloid Plaques
Atherosclerosis
Alzheimer Disease
Intracranial Arteriosclerosis
Vascular Dementia
Apolipoprotein E4
Dementia
Alleles
Vascular Diseases
Artifacts
Blood Vessels
Autopsy

Keywords

  • Alzheimer's disease
  • Apolipoprotein E
  • Atherosclerosis
  • Circle of Willis
  • Neuropathology
  • Risk factor

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Circle of Willis atherosclerosis : Association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles. / Beach, Thomas G.; Wilson, Jeffrey; Sue, Lucia I.; Newell, Amanda; Poston, Marissa; Cisneros, Raquel; Pandya, Yoga; Esh, Chera; Connor, Donald J.; Sabbagh, Marwan; Walker, Douglas G.; Roher, Alex E.

In: Acta Neuropathologica, Vol. 113, No. 1, 01.2007, p. 13-21.

Research output: Contribution to journalArticle

Beach, TG, Wilson, J, Sue, LI, Newell, A, Poston, M, Cisneros, R, Pandya, Y, Esh, C, Connor, DJ, Sabbagh, M, Walker, DG & Roher, AE 2007, 'Circle of Willis atherosclerosis: Association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles', Acta Neuropathologica, vol. 113, no. 1, pp. 13-21. https://doi.org/10.1007/s00401-006-0136-y
Beach, Thomas G. ; Wilson, Jeffrey ; Sue, Lucia I. ; Newell, Amanda ; Poston, Marissa ; Cisneros, Raquel ; Pandya, Yoga ; Esh, Chera ; Connor, Donald J. ; Sabbagh, Marwan ; Walker, Douglas G. ; Roher, Alex E. / Circle of Willis atherosclerosis : Association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles. In: Acta Neuropathologica. 2007 ; Vol. 113, No. 1. pp. 13-21.
@article{6beef7a50f264839babd66895b05241e,
title = "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-ε4 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-ε4 allele.",
keywords = "Alzheimer's disease, Apolipoprotein E, Atherosclerosis, Circle of Willis, Neuropathology, Risk factor",
author = "Beach, {Thomas G.} and Jeffrey Wilson and Sue, {Lucia I.} and Amanda Newell and Marissa Poston and Raquel Cisneros and Yoga Pandya and Chera Esh and Connor, {Donald J.} and Marwan Sabbagh and Walker, {Douglas G.} and Roher, {Alex E.}",
year = "2007",
month = "1",
doi = "10.1007/s00401-006-0136-y",
language = "English (US)",
volume = "113",
pages = "13--21",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Circle of Willis atherosclerosis

T2 - Association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles

AU - Beach, Thomas G.

AU - Wilson, Jeffrey

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.

PY - 2007/1

Y1 - 2007/1

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-ε4 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-ε4 allele.

AB - 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-ε4 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-ε4 allele.

KW - Alzheimer's disease

KW - Apolipoprotein E

KW - Atherosclerosis

KW - Circle of Willis

KW - Neuropathology

KW - Risk factor

UR - http://www.scopus.com/inward/record.url?scp=33751219894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751219894&partnerID=8YFLogxK

U2 - 10.1007/s00401-006-0136-y

DO - 10.1007/s00401-006-0136-y

M3 - Article

VL - 113

SP - 13

EP - 21

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

IS - 1

ER -