Deficits in Mitochondrial Spare Respiratory Capacity Contribute to the Neuropsychological Changes of Alzheimer's Disease
Deficits in Mitochondrial Spare Respiratory Capacity Contribute to the Neuropsychological Changes of Alzheimer's Disease
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DOI：
10.3390/jpm10020032
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发表时间：
2020-06-01
影响因子：
--
通讯作者：
Venneri, Annalena
中科院分区：
文献类型：
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作者：
Bell, Simon M.;De Marco, Matteo;Venneri, Annalena
阿尔茨海默病（AD）是使用神经心理学测试诊断的，由淀粉样蛋白和tau生物标志物和神经成像异常支持。神经心理学变化的原因尚不清楚，因为它们与生物标志物无关。本研究探讨了AD患者细胞代谢的变化是否与神经心理学变化相关。成纤维细胞取自10名AD患者和10名对照。代谢评估包括测量总细胞ATP、细胞外乳酸、线粒体膜电位（MMP）、线粒体呼吸和糖酵解功能。所有参与者都进行了神经心理测试和大脑结构MRI评估。AD患者的延迟回忆、即刻回忆、语义记忆、语音流畅性和简易精神状态检查（MMSE）评分均显著降低。AD患者的左海马、左顶叶、右顶叶和前内侧前额叶皮质灰质体积也明显较小。成纤维细胞MMP，线粒体备用呼吸能力（MSRC），糖酵解储备，和细胞外乳酸被发现在AD患者较低。MSRC/MMP与语义记忆、即时和延迟情景回忆显著相关。在控制了年龄、教育程度和脑储备后，MSRC和延迟情景回忆之间的相关性仍然显著。灰质体积与MRSC/MMP无相关性。AD成纤维细胞代谢评估可能代表AD的新出现的疾病生物标志物。
Alzheimer's disease (AD) is diagnosed using neuropsychological testing, supported by amyloid and tau biomarkers and neuroimaging abnormalities. The cause of neuropsychological changes is not clear since they do not correlate with biomarkers. This study investigated if changes in cellular metabolism in AD correlate with neuropsychological changes. Fibroblasts were taken from 10 AD patients and 10 controls. Metabolic assessment included measuring total cellular ATP, extracellular lactate, mitochondrial membrane potential (MMP), mitochondrial respiration and glycolytic function. All participants were assessed with neuropsychological testing and brain structural MRI. AD patients had significantly lower scores in delayed and immediate recall, semantic memory, phonemic fluency and Mini Mental State Examination (MMSE). AD patients also had significantly smaller left hippocampal, left parietal, right parietal and anterior medial prefrontal cortical grey matter volumes. Fibroblast MMP, mitochondrial spare respiratory capacity (MSRC), glycolytic reserve, and extracellular lactate were found to be lower in AD patients. MSRC/MMP correlated significantly with semantic memory, immediate and delayed episodic recall. Correlations between MSRC and delayed episodic recall remained significant after controlling for age, education and brain reserve. Grey matter volumes did not correlate with MRSC/MMP. AD fibroblast metabolic assessment may represent an emergent disease biomarker of AD.