Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer's disease: Metabolic basis for dementia

Jingshu Xu, Paul Begley, Stephanie J. Church, Stefano Patassini, Selina McHarg, Nina Kureishy, Katherine A. Hollywood, Henry J. Waldvogel, Hong Liu, Shaoping Zhang, Wanchang Lin, Karl Herholz, Clinton Turner, Beth J. Synek, Maurice A. Curtis, Jack Rivers-Auty, Catherine B. Lawrence, Katherine A B Kellett, Nigel M. Hooper, Emma R L C VardyDonghai Wu, Richard D. Unwin, Richard L M Faull, Garth J S Cooper*, Andrew Dowsey

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

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Abstract

Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer's disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem case-control study. Glucose, sorbitol and fructose were markedly elevated in all AD brain regions, whereas copper was correspondingly deficient throughout (all P <0.0001). In the ante-mortem case-control study, by contrast, plasma-glucose and plasma-copper levels did not differ between patients and controls. There were pervasive defects in regulation of glucose and copper in AD brain but no evidence for corresponding systemic abnormalities in plasma. Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD.
Original languageEnglish
Article number27524
Number of pages12
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 9 Jun 2016

Structured keywords

  • Jean Golding

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