Marsillach Judit, Adorni Maria Pia, Zimetti Francesca, Papotti Bianca, Zuliani Giovanni, Cervellati Carlo
Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
Unit of Neurosciences, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Antioxidants (Basel). 2020 Dec 3;9(12):1224. doi: 10.3390/antiox9121224.
Several lines of epidemiological evidence link increased levels of high-density lipoprotein-cholesterol (HDL-C) with lower risk of Alzheimer's disease (AD). This observed relationship might reflect the beneficial effects of HDL on the cardiovascular system, likely due to the implication of vascular dysregulation in AD development. The atheroprotective properties of this lipoprotein are mostly due to its proteome. In particular, apolipoprotein (Apo) A-I, E, and J and the antioxidant accessory protein paraoxonase 1 (PON1), are the main determinants of the biological function of HDL. Intriguingly, these HDL constituent proteins are also present in the brain, either from in situ expression, or derived from the periphery. Growing preclinical evidence suggests that these HDL proteins may prevent the aberrant changes in the brain that characterize AD pathogenesis. In the present review, we summarize and critically examine the current state of knowledge on the role of these atheroprotective HDL-associated proteins in AD pathogenesis and physiopathology.
多项流行病学证据表明，高密度脂蛋白胆固醇（HDL-C）水平升高与阿尔茨海默病（AD）风险降低相关。这种观察到的关系可能反映了HDL对心血管系统的有益作用，这可能是由于血管调节异常在AD发病过程中的影响。这种脂蛋白的抗动脉粥样硬化特性主要归因于其蛋白质组。特别是，载脂蛋白（Apo）A-I、E和J以及抗氧化辅助蛋白对氧磷酶1（PON1）是HDL生物学功能的主要决定因素。有趣的是，这些HDL组成蛋白也存在于大脑中，要么是原位表达，要么是来自外周。越来越多的临床前证据表明，这些HDL蛋白可能预防以AD发病机制为特征的大脑异常变化。在本综述中，我们总结并批判性地审视了目前关于这些抗动脉粥样硬化HDL相关蛋白在AD发病机制和生理病理学中作用的知识状态。
