Bell Simon M, De Marco Matteo, Barnes Katy, Shaw Pamela J, Ferraiuolo Laura, Blackburn Daniel J, Mortiboys Heather, Venneri Annalena
Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UK.
J Pers Med. 2020 Apr 29;10(2):32. doi: 10.3390/jpm10020032.
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.
阿尔茨海默病（AD）通过神经心理学测试进行诊断，并得到淀粉样蛋白、tau生物标志物及神经影像学异常结果的支持。神经心理学变化的原因尚不清楚，因为它们与生物标志物不相关。本研究调查了AD患者细胞代谢变化是否与神经心理学变化相关。从10例AD患者和10例对照者身上获取成纤维细胞。代谢评估包括测量细胞总ATP、细胞外乳酸、线粒体膜电位（MMP）、线粒体呼吸和糖酵解功能。所有参与者均接受神经心理学测试和脑结构MRI检查。AD患者在延迟和即时回忆、语义记忆、音素流畅性及简易精神状态检查表（MMSE）中的得分显著较低。AD患者左侧海马、左侧顶叶、右侧顶叶及前额叶内侧前部皮质的灰质体积也显著较小。研究发现，AD患者的成纤维细胞MMP、线粒体备用呼吸能力（MSRC）、糖酵解储备及细胞外乳酸水平较低。MSRC/MMP与语义记忆、即时和延迟情景记忆显著相关。在控制年龄、教育程度和脑储备后，MSRC与延迟情景记忆之间的相关性仍然显著。灰质体积与MRSC/MMP不相关。AD成纤维细胞代谢评估可能代表一种新兴的AD疾病生物标志物。
