Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.
Department of Analytical Chemistry, University of Chemistry and Technology, Prague, Czech Republic.
Clin Biochem. 2019 Oct;72:71-80. doi: 10.1016/j.clinbiochem.2019.04.003. Epub 2019 Apr 4.
Altered amyloid metabolism and mitochondrial dysfunction play key roles in the development of Alzheimer's disease (AD). We asked whether an association exists between disturbed platelet mitochondrial respiration and the plasma concentrations of Aβ and Aβ in patients with AD.
Plasma Aβ and Aβ concentrations and mitochondrial respiration in intact and permeabilized platelets were measured in 50 patients with AD, 15 patients with vascular dementia and 25 control subjects. A pilot longitudinal study was performed to monitor the progression of AD in a subgroup 11 patients with AD.
The mean Aβ, Aβ and Aβ/Aβ levels were not significantly altered in patients with AD compared with controls. The mitochondrial respiratory rate in intact platelets was significantly reduced in patients with AD compared to controls, particularly the basal respiratory rate, maximum respiratory capacity, and respiratory reserve; however, the flux control ratio for basal respiration was increased. A correlation between the plasma Aβ concentration and mitochondrial respiration in both intact and permeabilized platelets differs in controls and patients with AD.
Based on our data, (1) mitochondrial respiration in intact platelets, but not the Aβ level itself, may be included in a panel of biomarkers for AD; (2) dysfunctional mitochondrial respiration in platelets is not explained by changes in plasma Aβ concentrations; and (3) the association between mitochondrial respiration in platelets and plasma Aβ levels differs in patients with AD and controls. The results supported the hypothesis that mitochondrial dysfunction is the primary factor contributing to the development of AD.
淀粉样蛋白代谢和线粒体功能障碍的改变在阿尔茨海默病（AD）的发展中起着关键作用。我们想知道 AD 患者血小板线粒体呼吸功能紊乱与 Aβ和 Aβ在血浆中的浓度之间是否存在关联。
在 50 例 AD 患者、15 例血管性痴呆患者和 25 例对照者中，测定了血小板完整和通透状态下的 Aβ和 Aβ在血浆中的浓度和线粒体呼吸功能。对 11 例 AD 患者进行了亚组的前瞻性纵向研究，以监测 AD 的进展。
与对照组相比，AD 患者的平均 Aβ、Aβ在血浆中的浓度无明显改变。与对照组相比，AD 患者的血小板完整状态下的线粒体呼吸率明显降低，特别是基础呼吸率、最大呼吸能力和呼吸储备；然而，基础呼吸的通量控制比增加。在对照组和 AD 患者中，血浆 Aβ在完整和通透血小板中的浓度与线粒体呼吸之间的相关性不同。
根据我们的数据，（1）血小板完整状态下的线粒体呼吸，而不是 Aβ水平本身，可能被纳入 AD 的一组生物标志物中；（2）血小板中功能性线粒体呼吸功能障碍不能用血浆 Aβ浓度的变化来解释；（3）血小板中与线粒体呼吸相关的 Aβ在 AD 患者和对照组中的水平之间的相关性不同。这些结果支持了线粒体功能障碍是 AD 发展的主要因素的假说。
