Background: Hypercholesterolemia is known to increase the risk of AD in later life, the purpose of this study is to illustrate brain metabolic and structural changes in a cholesterol-fed rabbit model of Alzheimer's Disease (AD) by using clinical 3 T Magnetic Resonance Imaging (MRI).
Methods: The Institutional Animal Care and Use Committee of Zhejiang Chinese Medical University approved the study. Totally 16 Japanese White Rabbits (JWR) were randomly divided into 2 groups including normal control group fed with routine diet (group NC) and high cholesterol diet group (group CD) fed a 2% cholesterol diet with 0.24 ppm copper in the drinking water for 12 weeks. Magnetic resonance spectroscopy (MRS) and structural image of rabbit brain were performed by using a 3 Tesla (T) MRI scanner with an 8 channel Rabbit coil. The chemical metabolites were identified by LC Model including N-acetylaspartate (NAA), creatine (Cr), glutamate (Glu), glutamine (Gln), Glycerophosphatidylcholine (GPC), phosphorylcholine (PCH), and myoinositol (MI). The relative concentrations (/Cr) were analyzed. Additionally, Amyloid-β (Aβ) accumulation in the brain was measured postmortem. For comparisons of MR and Aβ data between groups, two-tailed t-tests were performed.
Results: The ratio of NAA/Cr (0.76 ± 0.10) and Glu/Cr (0.90 ± 0.14) in group CD were lower than those in the group NC (0.87 ± 0.06, 1.13 ± 0.22, respectively, P < 0.05). Compared to the group NC (2.88 ± 0.09 cm3, 0.63 ± 0.08 cm3, respectively), the cortical and hippocampal volumes (2.60 ± 0.14 cm3 and 0.47 ± 0.07 cm3, respectively) of rabbits brain decreased in the group CD while the third and lateral ventricular volumes enlarged (44.56 ± 6.01 mm3 vs 31.40 ± 6.14 mm3, 261.40 ± 30.98 mm3 vs 153.81 ± 30.08 mm3, P < 0.05). These metabolic and structural changes were additionally accompanied by the significant increase of Aβ1-42 in the cortex and hippocampus (163.60 ± 16.26 pg/mg and 215.20 ± 69.86 pg/mg, respectively, P < 0.05).
Conclusion: High cholesterol diet can induce the brain metabolic and structural changes of the rabbit including lowered level of NAA and Glu and the atrophy of the brain which were similar to those of human AD.
Keywords: Amyloid β; Brain metabolite; Cholesterol; Magnetic resonance imaging; Magnetic resonance spectroscopy; Rabbit.