Just before 2017 comes to an end the Ecole Polytechnique Fédérale de Lausanne published in Nature magazine the results of a study and experiments into the theory that Alzheimer’s could be a metabolic disease. During aging and disease such as Alzheimer’s, cells suffer increasing damage and struggle to protect themselves and replace dysfunctional mitochondria. Since mitochondria provide energy to brain cells, leaving them unprotected in Alzheimer’s disease favors brain damage, giving rise to symptoms like memory loss over the years.
During the research they found out that by boosting mitochondria defenses in an Alzheimer’s disease model they not only enabled them to protect themselves, but that it also reduced the formation of amyloid plaques. The scientists identified two defense mechanisms that keep mitochondria in shape. There is the so called “mitochondrial unfolded protein response” (UPRmt), which protects mitochondria from stress (which the same team reported on earlier, read here). Secondly, a process called mitophagy, that recycles defective mitochondria. Both are important to delaying or preventing excessive mitochondrial damage during disease.
Note: a disease model is an animal or cells displaying all or some of the disease pathological processes that are observed in the actual human or animal disease. Studying disease models aids understanding of how the disease develops and testing potential treatment approaches. It is however not the actual disease.
The researchers hypothized that activating the defense might tackle mitochondria that are dysfunctional in the brains of Alzheimer’s patients. The team started by testing well-established compounds, such as the antibiotic doxycycline and the vitamin nicotinamide riboside (NR), which can turn on the UPRmt and mitophagy defense systems in a worm model (C. elegans) of Alzheimer’s disease. They observed that health, performance and lifespan of worms exposed to the drugs increased remarkably compared with untreated worms. Plaque formation was also significantly reduced in the treated animals. The scientists observed similar improvements when they turned on the same mitochondrial defense pathways in cultured human neuronal cells, using the same drugs.
Based on this a test was setup to evaluate NR in a mouse model of Alzheimer’s disease. Again a significant improvement of mitochondrial function and a reduction in the number of amyloid plaques was observed. Moreover the scientists observed a clear recovery of the cognitive function in the mice.
In summary the study shows that in Alzheimer’s suffering mice restoring mitochondrial health reduces plaque formation and improves brain function, which is the objective of all Alzheimer’s researchers and patients. Next is to repeat the study in human patients. Considering that nicotinamide riboside is available in a stable and safe formulation (Niagen) on the market this study provides a glimmer of hope that this epidemic under the elderly can be slowed.