ApoB-100 transgenic mice were designed as a model of hyperlipidemia and atherosclerosis. Increasing evidence suggests that hypercholesterolemia and other vascular factors may contribute to the pathogenesis of late onset Alzheimer’s Disease (LOAD). ApoB is known as the primary apolipoprotein of cholesterol-carrying low-density lipoproteins (LDL) and triglyceride-rich very-low-density lipoproteins (VLDL). Atherosclerosis and AD patients share a very similar pathological plasma lipid profile, exhibiting increased levels of LDL along with decreased high-density lipoprotein (HDL) levels. Intriguingly, a post-mortem study of AD patients showed that LDL and ApoB levels positively correlate with brain Aβ42 levels .
ApoB-100 animals overexpress the entire 43 kb human apolipoprotein B-100 (ApoB-100) gene including its natural human promoter.
- Decreased learning and memory
- Increased total cholesterol and triglycerides
- Increased LDL but decreased HDL levels
- Increased lipid peroxidation
- Strong ApoB-100 accumulation at cerebral vessels
- Increased Aβ1-38, 1-40 and 1-42 levels
Figure 1. Increased cerebral lipid peroxidation as analyzed by MDA levels, the hippocampus of ApoB and nontransgenic (ntg) animals. n = 15 per group. Mean + SEM. Two-way ANOVA with Bonferroni’s post hoc test. *p<0.05; ***p<0.00.
Figure 2. Memory decline of ApoB-100 mice over age. Escape latency in the Morris water maze during 4 testing days of 12 month old animals. ApoB n = 23, ntg n = 22. Mean ± SEM. Two-way ANOVA with Bonferroni post hoc test. **p<0.01.