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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:2055.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Circle of Willis Atherosclerosis Is a Risk Factor for Sporadic Alzheimer’s Disease

Alex E. Roher; Chera Esh; Tyler A. Kokjohn; Walter Kalback; Dean C. Luehrs; James D. Seward; Lucia I. Sue; Thomas G. Beach

From the Longtine Center for Molecular Biology and Genetics (A.E.R., C.E., W.K., D.C.L.), Sun Health Research Institute, Sun City; Department of Microbiology (T.A.K.), School of Osteopathic Medicine, Midwestern University, Glendale; and Department of Epidemiology and Biostatistics (J.D.S.) and W. H. Civin Laboratory for Neuropathology (L.I.S.), Sun Health Research Institute, Sun City, Ariz.

Correspondence to Alex E. Roher, Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, 10515 W Santa Fe Dr, Sun City, AZ 85351. E-mail alex.roher{at}sunhealth.org

Objectives— We conducted a quantitative investigation of brain arterial atherosclerotic damage and its relationship to sporadic Alzheimer’s disease (AD).

Methods and Results— Fifty-four consecutive autopsy cases, 32 AD and 22 nondemented control subjects, were examined to establish the degree of arterial stenosis. Vessel external and lumenal area measurements were taken from 3-mm arterial cross-sections to calculate a stenosis index. AD patient circle of Willis arteries possessed a significant degree of stenosis as a consequence of multiple and severe atherosclerotic lesions. These lesions were significantly more severe in AD cases than in age-matched controls (P<0.0001), and the number of stenoses and the index of occlusion (R=0.67; P<0.00001) were positively correlated. In addition, the index of stenosis significantly correlated with the following measures of AD neuropathological lesions: total plaque score, neuritic plaque score, neurofibrillary tangle score, Braak stage score, and white matter rarefaction score.

Conclusions— Our study reveals an association between severe circle of Willis atherosclerosis and sporadic AD that should be considered a risk factor for this dementia. These observations strongly suggest that atherosclerosis-induced brain hypoperfusion contributes to the clinical and pathological manifestations of AD.

Key Words: atherosclerosis • circle of Willis • Alzheimer’s disease • brain hypoperfusion

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