Data obtained post-mortem in patients with Alzheimer's disease show an increase in the concentration of sodium in brain tissue. These local changes in sodium concentration would occur during the advanced phase of the disease and would be biomarkers of an early metabolic deficit correlated with cognitive decline.
With the exploitation of very high field MRI scanners, sodium (23Na) magnetic resonance imaging (MRI) is now a sufficiently mature technique to measure such changes, in vivo and non-invasively (see box).
A conclusive comparative analysis
Using this technique, researchers from BAOBAB and UNIACT (NeuroSpin department), in collaboration with teams from BioMaps (SHFJ et GHU Paris) and the University of Aachen (JARA-BRAIN, Forschungszentrum Jülich GmbH, Allemagne) quantitatively established a significant increase in tissue sodium concentration in 17 people with Alzheimer's disease (frome the SHATAU7/IMATAU cohort), compared to 22 healthy people of the same age in the control group (from the NeuroSpin SENIOR cohort). This increase is strongly related to the degree of disease progression, in particular the cognitive status of the patient, as well as to the load of phosphorylated tau protein imaged by positron emission tomography (with [18F] flortaucipir).
In question, the disruption of homeostasis?
Within neurons, sodium concentration is regulated by a transmembrane gradient maintained by the Na+/K+ pump, which stabilizes cells at their resting potential. This process is highly dependent on adenosine triphosphate (ATP) supplied by the mitochondria and is necessary for cell homeostasis and neuronal communication.
The accumulation of pathological aggregates of Tau and/or amyloid-β proteins would impair the functioning of the mitochondrial respiratory chain causing ATP deficiency, deregulation of ion channels and increasing disruption of transmembrane ion gradients. Generating an action potential would be energetically more and more costly for the neuron and would lead to dysfunctional neurotransmission and then to neurodegeneration.
By highlighting the correlation between the tissue concentration of sodium and the cognitive state of patients, this MRI technique is presented as a method of non-invasive early diagnosis or therapeutic follow-up. It would also become a way to study the link between the progression of functional alterations and the energy deficiency impacting neurotransmission.
Sodium MRI, a technique with high potential for the future
It is the use of very high fields, 7T or soon 11.7 T at NeuroSpin, which allows the development of MRI of so-called exotic nuclei, other than protons. By increasing the available signal, the detection and imaging of low concentration metabolites and electrolytes (of the order of mmol/L) becomes possible in a few minutes.
Sodium MRI has recently benefited from methodological and technological improvements allowing the improvement of its spatial and temporal resolutions and the quantification of tissue sodium concentrations. As a result, sodium MRI is becoming an increasingly attractive tool in clinical research to explore cellular homeostasis in the context of inflammatory or neurodegenerative diseases such as multiple sclerosis or Alzheimer's disease.
Fawzi Boumezbeur's team (BAOBAB/NeuroSpin) is developing metabolic imaging and in vivo magnetic resonance spectroscopy of nuclei of interest in medicine, biology or pharmacology such as proton (1H), carbon-13 (13C), lithium-7 (7Li), phosphorus (31P) and sodium (23Na) from rodents to humans.Contact Joliot Institute researcher:
Fawzi Boumezbeur (fawzi.boumezbeur@cea.fr)