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

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

Research output: Contribution to journalArticle (Academic Journal)peer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)851-7
Number of pages7
JournalJournal of Alzheimer's Disease
Volume44
Issue number3
DOIs
Publication statusPublished - 2015

Keywords

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease
  • Autopsy
  • Brain
  • Brain Chemistry
  • Case-Control Studies
  • Female
  • Humans
  • Lewy Body Disease
  • Male
  • Middle Aged
  • Plaque, Amyloid
  • Potassium
  • Severity of Illness Index
  • Sodium
  • Statistics, Nonparametric
  • Tandem Mass Spectrometry

Fingerprint

Dive into the research topics of 'Quantitative measurement of [Na+] and [K+] in postmortem human brain tissue indicates disturbances in subjects with Alzheimer's disease and dementia with Lewy bodies'. Together they form a unique fingerprint.

Cite this