Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Quantitative measurement of [Na+] and [K+] in postmortem human brain tissue indicates disturbances in subjects with Alzheimer's Disease and dementia with Lewy bodies
AU - Graham, Stewart F.
AU - Nasarauddin, Muhammad Bin
AU - Carey, Manus
AU - McGuinness, Bernadette
AU - Holscher, Christian
AU - Kehoe, Patrick G.
AU - Love, Seth
AU - Passmore, Anthony P.
AU - Elliott, Christopher T.
AU - Meharg, Andrew
AU - Green, Brian D.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - dementia with Lewy bodies
KW - human brain
KW - ICP-MS
KW - potassium
KW - sodium
U2 - 10.3233/JAD-141869
DO - 10.3233/JAD-141869
M3 - Journal article
C2 - 25362038
VL - 44
SP - 851
EP - 857
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 3
ER -