Background: Mitochondrial dysfunction is a pathological feature that manifests early in the brains of patients with Alzheimer’s Disease (AD). The disruption of mitochondrial dynamics contributes to mitochondrial morphological and functional impairments. Our previous study demonstrated that the expression of genes involved in amyloid beta generation was altered in the peripheral blood of AD patients.

Objective: The aim of this study was to further investigate the relative levels of mitochondrial genes involved in mitochondrial dynamics, including mitochondrial fission and fusion, and mitophagy in peripheral blood samples from patients with AD compared to healthy controls.

Methods: The mRNA levels were analyzed by real-time polymerase chain reaction. Gene expression profiles were assessed in relation to cognitive performance.

Results: Significant changes were observed in the mRNA expression levels of fission-related genes; Fission1 (FIS1) levels in AD subjects were significantly higher than those in healthy controls, whereas Dynamin- related protein 1 (DRP1) expression was significantly lower in AD subjects. The levels of the mitophagy-related genes, PTEN-induced kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3), were significantly increased in AD subjects and elderly controls compared to healthy young controls. The mRNA levels of Parkin (PARK2) were significantly decreased in AD. Correlations were found between the expression levels of FIS1, DRP1 and PARK2 and cognitive performance scores.

Conclusion: Alterations in mitochondrial dynamics in the blood may reflect impairments in mitochondrial functions in the central and peripheral tissues of AD patients. Mitochondrial fission, together with mitophagy gene profiles, might be potential considerations for the future development of blood-based biomarkers for AD.

背景：线粒体功能障碍是一种病理特征，在阿尔茨海默病 (AD) 患者的大脑中早期表现出来。线粒体动力学的破坏导致线粒体形态和功能障碍。我们之前的研究表明，AD 患者外周血中参与淀粉样蛋白 β 生成的基因表达发生了改变。

目的：本研究的目的是进一步研究与健康对照相比，AD 患者外周血样本中参与线粒体动力学（包括线粒体裂变和融合以及线粒体自噬）的线粒体基因的相对水平。

方法：通过实时聚合酶链反应分析mRNA水平。评估与认知表现相关的基因表达谱。

结果：裂变相关基因mRNA表达水平发生显着变化；AD 受试者的 Fission1 (FIS1) 水平显着高于健康对照组，而 AD 受试者的动力蛋白相关蛋白 1 (DRP1) 表达显着降低。与健康的年轻对照相比，AD 受试者和老年对照的线粒体自噬相关基因、PTEN 诱导的激酶 1 (PINK1) 和微管相关蛋白 1 轻链 3 (LC3) 的水平显着增加。AD中Parkin（PARK2）的mRNA水平显着降低。发现 FIS1、DRP1 和 PARK2 的表达水平与认知表现评分之间存在相关性。

结论：血液中线粒体动力学的改变可能反映了 AD 患者中枢和外周组织线粒体功能的损伤。线粒体裂变以及线粒体自噬基因谱，可能是未来开发基于血液的 AD 生物标志物的潜在考虑因素。