Unlocking the Metabolic Drivers of Alzheimer’s Disease
Cellular oxygen consumption in the brain may shed new light on Alzheimer’s disease onset, progression, and treatment.
Understanding mitochondrial metabolism may change how Alzheimer’s disease is identified and treated. Sarah Flowers, a neuroscientist at the University of Virginia, measures oxygen consumption to understand what is happening in brain cells.
Why are oxygen consumption measurements important in Alzheimer’s disease research?
Treating Alzheimer’s disease after the onset of amyloid and tau protein accumulation is difficult. However, a metabolism deficit occurs in the brain before protein accumulation, and this could be a target for early intervention. As such, we are interested in how mitochondrial metabolism is affected by Alzheimer’s disease risk factors or in Alzheimer’s disease itself. We focus specifically on oxygen consumption in astrocytes because they are the metabolic drivers of the brain.
What technical challenges are there for measuring oxygen consumption?
A lot of technologies are good for measuring different parameters at a single timepoint, but we were looking for something that could evaluate longitudinal cellular responses. We found the Resipher instrument, which can monitor samples and measure oxygen consumption over weeks and months. Importantly, it integrated with our cell culture system—we did not have to change our media, plates, or incubators. This was vital because metabolism is affected by so many things, and so it was critical for us to measure oxygen consumption in cells in their normal environments.
How has the ability to make longitudinal measurements affected your research?
We know that apolipoprotein E (APOE) genotype influences anti-Alzheimer’s drug effectiveness. Our experiments show that some therapeutics are more helpful with the APOE3 genotype while others are more useful against the APOE4 variant. By understanding the fundamental differences between these genotypes, we hope to enable more personalized, targeted therapeutics. I think these avenues of investigation are opening up possibilities for therapeutics that might be helpful at very early stages of Alzheimer’s disease.
Learn more about longitudinal measurements of oxygen consumption.
This interview has been condensed and edited for clarity.
What obstacles do you face when trying to measure cellular metabolism?
