Large vessel cerebral atherosclerosis is not in direct association with neuropathological lesions of Alzheimer's disease.
BACKGROUND
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 epsilon4 (APOE epsilon4) 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 epsilon4 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 epsilon4 allele (p = 0.072).


CONCLUSIONS
Our results suggest that cerebral large vessel atherosclerosis is not in direct association with APs or NFTs - hallmarks of AD neuropathology.
Luoto
Teemu M
TM
Department of Forensic Medicine, University of Tampere, Tampere, Finland. Teemu.Luoto@uta.fi
Haikonen
Satu
S
Haapasalo
Hannu
H
Goebeler
Sirkka
S
Huhtala
Heini
H
Erkinjuntti
Timo
T
Karhunen
Pekka J
PJ
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002941:Circle of Willis / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D002537:Intracranial Arteriosclerosis / Q000235:genetics / Q000473:pathology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000473:pathology*; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology*; D012737:Sex Factors
D053327:Apolipoprotein E4