Kosicek Marko, Hecimovic Silva
Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb, Croatia.
Int J Mol Sci. 2013 Jan 10;14(1):1310-22. doi: 10.3390/ijms14011310.
Brain is one of the richest organs in lipid content. Phospholipids (glycerophospholipids and sphingolipids) are important building blocks of cell membranes, which provide an optimal environment for protein interactions, trafficking and function. Because of that, alterations in their cellular levels could lead to different pathogenic processes in the brain, such as in Alzheimer's disease (AD), the most common type of dementia among older populations. There is increasing evidence that phospholipid changes occur during pathogenic processes in AD. It is known that lipids are tightly connected with metabolism of the Amyloid Precursor Protein (APP), which produces Amyloid-beta peptide (Aβ), the main component of senile plaques, which represent the main pathological hallmark of AD. However, the mechanism(s) of the lipid-effect on Aβ metabolism and AD pathogenesis is still not completely understood. This review summarizes the current knowledge on phospholipid changes occurring during normal aging and discusses phospholipid changes in the human brain associated with different stages of AD, as well changes in the cerebrospinal fluid and blood/plasma, which are interesting potential biomarkers for AD diagnosis and disease monitoring. At the end, we have discussed future perspectives of phospholipid changes as potential biomarkers and as targets for development of novel treatment strategies against AD.
大脑是脂质含量最丰富的器官之一。磷脂（甘油磷脂和鞘脂）是细胞膜的重要组成部分，为蛋白质相互作用、运输和功能提供了最佳环境。正因如此，其细胞水平的改变可能会导致大脑中不同的致病过程，比如在老年人群中最常见的痴呆类型——阿尔茨海默病（AD）中。越来越多的证据表明，在AD的致病过程中会发生磷脂变化。众所周知，脂质与淀粉样前体蛋白（APP）的代谢紧密相关，APP会产生β淀粉样肽（Aβ），而Aβ是老年斑的主要成分，老年斑是AD的主要病理标志。然而，脂质对Aβ代谢和AD发病机制的影响仍未完全明确。本综述总结了正常衰老过程中磷脂变化的现有知识，并讨论了与AD不同阶段相关的人类大脑中的磷脂变化，以及脑脊液和血液/血浆中的变化，这些都是AD诊断和疾病监测中有趣的潜在生物标志物。最后，我们讨论了磷脂变化作为潜在生物标志物以及作为开发抗AD新治疗策略靶点的未来前景。
