Bell, S.M., De Marco, M., Barnes, K. et al. (5 more authors) (2020) Deficits in mitochondrial spare respiratory capacity contribute to the neuropsychological changes of alzheimer’s disease. Journal of Personalized Medicine, 10 (2). 32. ISSN 2075-4426
Abstract
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.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2020 The Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Alzheimer’s disease; mitochondrial spare respiratory capacity; mitochondrial; membrane potential; glycolytic reserve; semantic memory; phonemic fluency; episodic memory; neuropsychology; neuroimaging |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number ALZHEIMER'S RESEARCH UK ARUK-NC2016-YOR PARKINSON'S UK F-1301 ALZHEIMER'S RESEARCH UK ARUK-PCRF2016A-1 WELLCOME TRUST (THE) UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 May 2020 10:33 |
Last Modified: | 04 May 2020 10:33 |
Status: | Published |
Publisher: | MDPI AG |
Refereed: | Yes |
Identification Number: | 10.3390/jpm10020032 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:160089 |