Cholesterol increases ventricular volume in a rabbit model of Alzheimer's disease.
One of the hallmarks of Alzheimer's disease is a significant increase in ventricular volume. To date we and others have shown that a cholesterol-fed rabbit model of Alzheimer's disease displays as many as fourteen different pathological markers of Alzheimer's disease including amyloid-β accumulation, thioflavin-S staining, blood brain barrier breach, microglia activation, cerebrovasculature changes, and alterations in learning and memory. Using structural magnetic resonance imaging at 3T, we now report that cholesterol-fed rabbits also show a significant increase in ventricular volume following 10 weeks on a diet of 2% cholesterol. The increase in volume is attributable in large part to increases in the size of the third ventricle. These changes are accompanied by significant increases in the number of amyloid-β immuno-positive cells in the cortex and hippocampus. Increases in the number of amyloid-β neurons in the cortex also occurred with the addition of 0.24 ppm copper to the drinking water. Together with a list of other pathological markers, the current results add further validity to the value of the cholesterol-fed rabbit as a non-transgenic animal model of Alzheimer's disease.
Department of Physiology and Pharmacology and the Blanchette Rockefeller Neurosciences Institute, West Virginia University, Morgantown, WV 26506, USA. bschreurs@hsc.wvu.edu
Stephen
S
Deci
Susan K
SK
Lemieux
Carrie A
CA
Smith-Bell
D Larry
DL
Sparks
Bernard G
BG
Schreurs
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D004195:Disease Models, Animal; D021621:Imaging, Three-Dimensional; D020547:Lateral Ventricles / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000378:metabolism; D011817:Rabbits
D016229:Amyloid beta-Peptides; D002791:Cholesterol, Dietary; D002784:Cholesterol