| First Author | Cui Y | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 3 | Pages | 1298-308 |
| PubMed ID | 21356380 | Mgi Jnum | J:169682 |
| Mgi Id | MGI:4941656 | Doi | 10.1016/j.ajpath.2010.11.057 |
| Citation | Cui Y, et al. (2011) Genetic Ablation of Apolipoprotein A-IV Accelerates Alzheimer's Disease Pathogenesis in a Mouse Model. Am J Pathol 178(3):1298-308 |
| abstractText | The link between lipoprotein metabolism and Alzheimer's disease (AD) has been established. Apolipoprotein A-IV (apoA-IV), a component of lipoprotein particles similar to apolipoprotein E, has been suggested to play an important role in brain metabolism. Although there are clinical debates on the function of its polymorphism in AD, the pathologic role of apoA-IV in AD is still unknown. Here, we report that genetic ablation of apoA-IV is able to accelerate AD pathogenesis in mice. In a mouse model that overexpresses human amyloid precursor protein (APP) and presenilin 1, genetic reduction of apoA-IV augments extracellular amyloid-beta peptide (Abeta) burden and aggravates neuron loss in the brain. In addition, genetic ablation of apoA-IV also accelerates spatial learning deficits and increases the mortality of mice. We have found that apoA-IV colocalizes within Abeta plaques in APP/presenilin 1 transgenic mice and binds to Abeta in vitro. Subsequent studies show that apoA-IV in this model facilitates Abeta uptake in the Abeta clearance pathway mediated by astrocytes rather than the amyloidogenic pathway of APP processing. Taken together, we conclude that apoA-IV deficiency increases Abeta deposition and results in cognitive damage in the mouse model. Enhancing levels of apoA-IV may have therapeutic potential in AD treatment. |
