Large Vessel Cerebral Atherosclerosis Is Not in Direct Association with Neuropathological Lesions of Alzheimer's Disease

Introduction: Cerebral hypoperfusion caused by large vessel atherosclerosis has been suggested to be associated with the pathogenesis of sporadic Alzheimer's disease (AD). Atherosclerosis and AD share risk factors such as age, diabetes, hypercholesterolemia, hypertension and apolipoprotein E epsilon 4 (APOE epsilon 4) allele. We studied the association between atherosclerosis of the circle of Willis (CW) and AD neuropathology in a large autopsy sample. Methods: The present study comprised a consecutive autopsy series (n = 466) representing noninstitutionalized general population aged 50 years and over (mean 70.8, SD 11.5 years). The atherosclerosis of CW was scored semiquantitatively and the amyloid plaque (AP) load in the frontal cortex and the number of neurofibrillary tangles (NFT) in the hippocampus were measured. Results: In a linear regression model, AP percentage area was associated with age (p < 0.0001) and APOE epsilon 4 allele (p < 0.0001), but not with CW score (p = 0.70) or gender (p = 0.11). Similarly, the NFT count was predicted only by age (p > 0.0001), and not by CW score (p = 0.36), gender (p = 0.41) or APOE epsilon 4 allele (p = 0.072). Conclusion: Our results suggest that cerebral large vessel atherosclerosis is not in direct association with APs or NFTs - hallmarks of AD neuropathology. Copyright (C) 2009 S. Karger AG, Basel