Kamat P K, Vacek J C, Kalani A, Tyagi N
Department of Physiology and Biophysics, School of Medicine, University of Louisville, and Louisville, KY 40202, USA.
Open Neurol J. 2015 Jun 24;9:9-14. doi: 10.2174/1874205X01509010009. eCollection 2015.
A high serum level of homocysteine, known as hyperhomocystenemia (HHcy) is associated with vascular dysfunction such as altered angiogenesis and increased membrane permeability. Epidemiological studies have found associations between HHcy and Alzheimer's disease (AD) progression that eventually leads to vascular dementia (VaD). VaD is the second most common cause of dementia in people older than 65, the first being AD. VaD affects the quality of life for those suffering by drastically decreasing their cognitive function. VaD, a cerebrovascular disease, generally occurs due to cerebral ischemic events from either decreased perfusion or hemorrhagic lesions. HHcy is associated with the hallmarks of dementia such as tau phosphorylation, Aβ aggregation, neurofibrillary tangle (NFT) formation, neuroinflammation, and neurodegeneration. Previous reports also suggest HHcy may promote AD like pathology by more than one mechanism, including cerebral microangiopathy, endothelial dysfunction, oxidative stress, neurotoxicity and apoptosis. Despite the corelations presented above, the question still exists - does homocysteine have a causal connection to AD? In this review, we highlight the role of HHcy in relation to AD by discussing its neurovascular effects and amelioration with dietary supplements. Moreover, we consider the studies using animal models to unravel the connection of Hcy to AD.
血清高同型半胱氨酸水平,即高同型半胱氨酸血症(HHcy),与血管功能障碍有关,如血管生成改变和膜通透性增加。流行病学研究发现,HHcy与阿尔茨海默病(AD)进展之间存在关联,最终导致血管性痴呆(VaD)。VaD是65岁以上人群中第二常见的痴呆病因,第一是AD。VaD通过大幅降低认知功能,影响患者的生活质量。VaD作为一种脑血管疾病,通常由于灌注减少或出血性病变引起的脑缺血事件而发生。HHcy与痴呆的特征有关,如tau蛋白磷酸化、Aβ聚集、神经原纤维缠结(NFT)形成、神经炎症和神经退行性变。先前的报告还表明,HHcy可能通过多种机制促进类似AD的病理过程,包括脑微血管病变、内皮功能障碍、氧化应激、神经毒性和细胞凋亡。尽管有上述相关性,但问题仍然存在——同型半胱氨酸与AD有因果关系吗?在这篇综述中,我们通过讨论HHcy的神经血管效应以及膳食补充剂对其的改善作用,强调了HHcy在AD中的作用。此外,我们考虑了使用动物模型来揭示同型半胱氨酸与AD之间联系的研究。