The brain is deeply dependent on lipid (fatty molecule) metabolism for proper development and function. Could abnormal lipid metabolism affect the brain’s stem cell population? Oh yes.
Karl J.L. Fernandez and his coworkers from the Research Center of the University of Montreal Hospital in Montreal, Canada and other collaborators has shown that neural stem cell populations in the brain can be compromised by abnormal lipid metabolism and that such abnormalities are characteristic of Alzheimer’s disease.
3xTg-AD mice form plaques in their brains that are similar to those in the brains of Alzheimer’s disease patients. Fernandez and his colleagues discovered that 3xTg-AD mice accumulate lipids within ependymal cells, which line the ventricles of the brain and serve as the main support cell of the forebrain Neural Stem Cells (NSCs). Interestingly, brains from Alzheimer’s disease patients, when examined after death also showed the accumulation of lipids within the same cell population.
When these lipids were examined further, it was clear that they were oleic acid-enriched fats (oleic acid is found in olive oil). In fact, injecting oleic acid into this area of the brain could recapitulate this pathology. When Fernandez and others inhibited oleic acid synthesis, they were able to fix the stem cell issues in the 3xTg-AD mice.
This fascinating study shows that the pathology in Alzheimer’s disease might be caused by perturbation of fatty acid metabolism in the stem cell niche that suppresses the regenerative functions of NSCs. Preventing accumulation of these fats in the cells surrounding the NSC population can potentially fix the stem cell abnormalities in patients with Alzheimer’s disease.
This study was published in the journal Cell Stem Cell.