Alterations of Alzheimer's disease in the cholesterol-fed rabbit, including vascular inflammation. Preliminary observations.
We determined the levels of endothelial inflammation using MECA-32 antibody and alpha 4 nicotinic receptor subunit densities employing [3H]epibatidine binding in the brains of Alzheimer's disease (AD) patients, cholesterol-fed rabbits, and appropriate controls. We also assessed rabbit brain for beta-amyloid levels and immunohistochemical localization, and for evidence of blood-brain barrier breach using normally-excluded Evans Blue dye. Dietary cholesterol induced a twofold increase in beta-amyloid concentration in rabbit hippocampal cortex, which may be related to the appearance of beta-amyloid immunoreactivity in the neuropil. Epibatidine binding was significantly decreased in AD superior frontal cortex, but unchanged in the superior frontal cortex of cholesterol-fed rabbits. Increased vascular MECA-32 immunoreactivity occurred in AD and cholesterol-fed rabbit brain. Evans Blue dye could be found in the parenchyma of cholesterol-fed rabbits only, and appeared as pockets of dye surrounding small blood vessels. The data suggest that vascular inflammation can lead to breach of the blood-brain barrier, which may produce biochemical derangements in surrounding brain tissue that are conducive to production of beta-amyloid.
Sparks
D L
DL
Sun Health Research Institute, Sun City, Arizona, USA. Lsparks@mail.sunhealth.org
Kuo
Y M
YM
Roher
A
A
Martin
T
T
Lukas
R J
RJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics; D002791:Cholesterol, Dietary; D004730:Endothelium, Vascular / Q000473:pathology*; D005625:Frontal Lobe / Q000098:blood supply / Q000473:pathology; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology; D006801:Humans; D007249:Inflammation; D011725:Pyridines / Q000493:pharmacokinetics; D011817:Rabbits; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000032:analysis; D014316:Tritium
D000954:Antigens, Surface; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002791:Cholesterol, Dietary; D011725:Pyridines; D011978:Receptors, Nicotinic; D014316:Tritium; C095910:MECA-32 antigen, mouse; C082748:epibatidine