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Published Online
on September 25, 2003

Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print September 25, 2003, doi: 10.1161/01.ATV.0000095973.42032.44
A more recent version of this article appeared on November 1, 2003
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Submitted on August 18, 2003
Accepted on September 4, 2003

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; ; and 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 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.

* To whom correspondence should be addressed. 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 image-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 and 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: PLEASE • SUPPLY • KEY • WORDS




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