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Deficits in Mitochondrial Spare Respiratory Capacity Contribute to the Neuropsychological Changes of Alzheimer’s Disease

Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UK
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These two authors are joint senior authors.
J. Pers. Med. 2020, 10(2), 32; https://doi.org/10.3390/jpm10020032
Received: 30 March 2020 / Revised: 20 April 2020 / Accepted: 24 April 2020 / Published: 29 April 2020
(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)
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. View Full-Text
Keywords: Alzheimer’s disease; mitochondrial spare respiratory capacity; mitochondrial; membrane potential; glycolytic reserve; semantic memory; phonemic fluency; episodic memory; neuropsychology; neuroimaging Alzheimer’s disease; mitochondrial spare respiratory capacity; mitochondrial; membrane potential; glycolytic reserve; semantic memory; phonemic fluency; episodic memory; neuropsychology; neuroimaging
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Bell, S.M.; De Marco, M.; Barnes, K.; Shaw, P.J.; Ferraiuolo, L.; Blackburn, D.J.; Mortiboys, H.; Venneri, A. Deficits in Mitochondrial Spare Respiratory Capacity Contribute to the Neuropsychological Changes of Alzheimer’s Disease. J. Pers. Med. 2020, 10, 32.

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