TY - JOUR
T1 - Rubidium and potassium levels are altered in Alzheimer's disease brain and blood but not in cerebrospinal fluid
AU - Roberts, Blaine R.
AU - Doecke, James D.
AU - Rembach, Alan
AU - Yévenes, L. Fernanda
AU - Fowler, Christopher J.
AU - McLean, Catriona A.
AU - Lind, Monica
AU - Volitakis, Irene
AU - Masters, Colin L.
AU - Bush, Ashley I.
AU - Hare, Dominic J.
AU - the Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group
N1 - Funding Information:
We wish to acknowledge the support of the Cooperative Research Centre (CRC) for Mental Health. The CRC programme is an Australian Government initiative. Tissues were received from the Victorian Brain Bank Network, supported by The University of Melbourne, Alfred Hospital, the Victorian Forensic Institute of Medicine, the National Health and Medical Research Council. We acknowledge funding from the Victorian Government’s Operational Infrastructure Support Program and the Australian Research Council Linkage Projects Scheme (with Agilent Technologies). Partial support from the National Health and Medical Research Council and the Alzheimer’s Drug Discovery Research Foundation.
PY - 2016/11/14
Y1 - 2016/11/14
N2 - Loss of intracellular compartmentalization of potassium is a biochemical feature of Alzheimer's disease indicating a loss of membrane integrity and mitochondrial dysfunction. We examined potassium and rubidium (a biological proxy for potassium) in brain tissue, blood fractions and cerebrospinal fluid from Alzheimer's disease and healthy control subjects to investigate the diagnostic potential of these two metal ions. We found that both potassium and rubidium levels were significantly decreased across all intracellular compartments in the Alzheimer's disease brain. Serum from over 1000 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL), showed minor changes according to disease state. Potassium and rubidium levels in erythrocytes and cerebrospinal fluid were not significantly different according to disease state, and rubidium was slightly decreased in Alzheimer's disease patients compared to healthy controls. Our data provides evidence that contrasts the hypothesized disruption of the blood-brain barrier in Alzheimer's disease, with the systemic decrease in cortical potassium and rubidium levels suggesting influx of ions from the blood is minimal and that the observed changes are more likely indicative of an internal energy crisis within the brain. These findings may be the basis for potential diagnostic imaging studies using radioactive potassium and rubidium tracers.
AB - Loss of intracellular compartmentalization of potassium is a biochemical feature of Alzheimer's disease indicating a loss of membrane integrity and mitochondrial dysfunction. We examined potassium and rubidium (a biological proxy for potassium) in brain tissue, blood fractions and cerebrospinal fluid from Alzheimer's disease and healthy control subjects to investigate the diagnostic potential of these two metal ions. We found that both potassium and rubidium levels were significantly decreased across all intracellular compartments in the Alzheimer's disease brain. Serum from over 1000 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL), showed minor changes according to disease state. Potassium and rubidium levels in erythrocytes and cerebrospinal fluid were not significantly different according to disease state, and rubidium was slightly decreased in Alzheimer's disease patients compared to healthy controls. Our data provides evidence that contrasts the hypothesized disruption of the blood-brain barrier in Alzheimer's disease, with the systemic decrease in cortical potassium and rubidium levels suggesting influx of ions from the blood is minimal and that the observed changes are more likely indicative of an internal energy crisis within the brain. These findings may be the basis for potential diagnostic imaging studies using radioactive potassium and rubidium tracers.
UR - https://www.scopus.com/pages/publications/85027459390
U2 - 10.1186/s40478-016-0390-8
DO - 10.1186/s40478-016-0390-8
M3 - Article
C2 - 27842602
AN - SCOPUS:85027459390
SN - 2051-5960
VL - 4
JO - Acta Neuropathologica Communications
JF - Acta Neuropathologica Communications
IS - 1
M1 - 119
ER -