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

Graham, Stewart F. and Nasarauddin, Muhammad Bin and Carey, Manus and McGuinness, Bernadette and Holscher, Christian and Kehoe, Patrick G. and Love, Seth and Passmore, Anthony P. and Elliott, Christopher T. and Meharg, Andrew and Green, Brian D. (2015) Quantitative measurement of [Na+] and [K+] in postmortem human brain tissue indicates disturbances in subjects with Alzheimer's Disease and dementia with Lewy bodies. Journal of Alzheimer's Disease, 44 (3). pp. 851-857. ISSN 1387-2877

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.