title: Quantitative measurement of [Na+] and [K+] in postmortem human brain tissue indicates disturbances in subjects with Alzheimer's disease and dementia with Lewy bodies.
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.
authors.affiliation: Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Stranmillis Road, Belfast, UK.
authors.forename: Stewart F
authors.initials: SF
authors.lastname: Graham
authors.affiliation: Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Stranmillis Road, Belfast, UK.
authors.forename: Muhammad Bin
authors.initials: MB
authors.lastname: Nasarauddin
authors.affiliation: Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Stranmillis Road, Belfast, UK.
authors.forename: Manus
authors.initials: M
authors.lastname: Carey
authors.affiliation: Department of Geriatric Medicine, Queen's University Belfast, Belfast, UK.
authors.forename: Bernadette
authors.initials: B
authors.lastname: McGuinness
authors.affiliation: Division of Biomedical Sciences and Life Sciences, Lancaster University, Lancaster, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Holscher
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Level 1 Learning and Research, Southmead Hospital, Bristol, UK.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Level 1 Learning and Research, Southmead Hospital, Bristol, UK.
authors.forename: Seth
authors.initials: S
authors.lastname: Love
authors.affiliation: Department of Geriatric Medicine, Queen's University Belfast, Belfast, UK.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Passmore
authors.affiliation: Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Stranmillis Road, Belfast, UK.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Elliott
authors.affiliation: Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Stranmillis Road, Belfast, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Meharg
authors.affiliation: Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Stranmillis Road, Belfast, UK.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Green
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001344:Autopsy; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000473:pathology; D011188:Potassium / Q000378:metabolism*; D012720:Severity of Illness Index; D012964:Sodium / Q000378:metabolism*; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry
chemical_list: D012964:Sodium; D011188:Potassium
keywords: Alzheimer's disease; ICP-MS; dementia with Lewy bodies; human brain; potassium; sodium