title: Rubidium and potassium levels are altered in Alzheimer's disease brain and blood but not in cerebrospinal fluid.
abstract: 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.
authors.affiliation: The Florey Institute of Neuroscience, The University of Melbourne, Parkville, VIC, Australia. blaine.roberts@florey.edu.au.|Cooperative Research Centre for Mental Health, Parkville, VIC, Australia. blaine.roberts@florey.edu.au.
authors.forename: Blaine R
authors.initials: BR
authors.lastname: Roberts
authors.affiliation: Cooperative Research Centre for Mental Health, Parkville, VIC, Australia.|The Australian e-Health Research Centre, Herston, QLD, Australia.|CSIRO Preventative Health Flagship, Molecular Science and Engineering, Parkville, VIC, Australia.
authors.forename: James D
authors.initials: JD
authors.lastname: Doecke
authors.affiliation: The Florey Institute of Neuroscience, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Rembach
authors.affiliation: The Florey Institute of Neuroscience, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: L Fernanda
authors.initials: LF
authors.lastname: Yévenes
authors.affiliation: The Florey Institute of Neuroscience, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
authors.affiliation: The Florey Institute of Neuroscience, The University of Melbourne, Parkville, VIC, Australia.|Department of Anatomical Pathology, The Alfred Hospital, Melbourne, VIC, Australia.|Department of Medicine, Central Clinical School, Monash University, Clayton, VIC, Australia.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.affiliation: The Florey Institute of Neuroscience, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Monica
authors.initials: M
authors.lastname: Lind
authors.affiliation: The Florey Institute of Neuroscience, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Irene
authors.initials: I
authors.lastname: Volitakis
authors.affiliation: The Florey Institute of Neuroscience, The University of Melbourne, Parkville, VIC, Australia.|Cooperative Research Centre for Mental Health, Parkville, VIC, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: The Florey Institute of Neuroscience, The University of Melbourne, Parkville, VIC, Australia.|Cooperative Research Centre for Mental Health, Parkville, VIC, Australia.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: The Florey Institute of Neuroscience, The University of Melbourne, Parkville, VIC, Australia.|Elemental Bio-imaging Facility, University of Technology, Broadway, Sydney, NSW, Australia.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Hare
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics; D001315:Australia; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D011188:Potassium / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism*; D013129:Spinal Puncture
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D012413:Rubidium; D011188:Potassium