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Quantitative measurement of [Na+] and [K+] in postmortem human brain tissue indicates disturbances in subjects with Alzheimer's Disease and dementia with Lewy bodies

Research output: Contribution to journalJournal article

Published
  • Stewart F. Graham
  • Muhammad Bin Nasarauddin
  • Manus Carey
  • Bernadette McGuinness
  • Christian Holscher
  • Patrick G. Kehoe
  • Seth Love
  • Anthony P. Passmore
  • Christopher T. Elliott
  • Andrew Meharg
  • Brian D. Green
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<mark>Journal publication date</mark>2015
<mark>Journal</mark>Journal of Alzheimer's Disease
Issue number3
Volume44
Number of pages7
Pages (from-to)851-857
Publication statusPublished
Early online date31/10/14
Original languageEnglish

Abstract

Alzheimer's disease (AD) is associated with significant disturbances in the homeostasis of Na+ and K+ ions as well as reduced levels of Na+/K+ ATPase in the brain. This study used ICP-MS to accurately quantify Na+ and K+ concentrations in human postmortem brain tissue. We analyzed parietal cortex (Brodmann area 7) from 28 cognitively normal age-matched controls, 15 cases of moderate AD, 30 severe AD, and 15 dementia with Lewy bodies (DLB). Associations were investigated between [Na+] and [K+] and a number of variables including diagnosis, age, gender, Braak tangle stage, amyloid-β (Aβ) plaque load, tau load, frontal tissue pH, and APOE genotype. Brains from patients with severe AD had significantly higher (26%; p < 0.001) [Na+] (mean 65.43 ± standard error 2.91 mmol/kg) than controls, but the concentration was not significantly altered in moderate AD or DLB. [Na+] correlated positively with Braak stage (r = 0.45; p < 0.0001), indicating association with disease severity. [K+] in tissue was 10% lower (p < 0.05) in moderate AD than controls. However, [K+] in severe AD and DLB (40.97 ± 1.31 mmol/kg) was not significantly different from controls. There was a significant positive correlation between [K+] and Aβ plaque load (r = 0.46; p = 0.035), and frontal tissue pH (r = 0.35; p = 0.008). [Na+] was not associated with [K+] across the groups, and neither ion was associated with tau load or APOE genotype. We have demonstrated disturbances of both [Na+] and [K+] in relation to the severity of AD and markers of AD pathology, although it is possible that these relate to late-stage secondary manifestations of the disease pathology.