How can exercise "cleanse" the brain of Alzheimer's?

For the 50 million people worldwide suffering from Alzheimer's disease, announcements by pharmaceutical giants announced earlier this year that they will end therapeutic treatment research have been devastating. The news is even more devastating given forecasts that 100 million more people will be diagnosed with Alzheimer's disease worldwide by 2050, all without any medical means to improve their quality of life.

It turns out however that the search for a treatment has been vital. New research shows that exercise can "cleanse" hostile environments in the brain of Alzheimer's mice, allowing new nerve cells in the hippocampus, the brain structure involved in memory and learning, to enable cognitive improvements, such as learning and memory. These results imply that pharmacological agents that enrich the hippocampal environment to stimulate cell growth and survival may be effective in restoring brain health and function in patients with Alzheimer's disease.

The brain of an individual with Alzheimer's disease is a hostile place, filled with the accumulation of unwanted nerve cell waste – amyloid plaques and neurofibrillary tangles – and a dramatic loss of nerve cells and connections leading to a decline. severe cognitive, such as memory loss. Targeting and disrupting this harmful junk food, especially amyloid plaques, to restore brain function has been the basis of many unsuccessful clinical trials. This futility led to a reassessment of the amyloid hypothesis, the central dogma of the pathology of Alzheimer's disease, based on the toxic accumulation of amyloid plaques.

At the same time, physical exercise has been shown to play a preventive role in Alzheimer's disease, but the way this is done and the way it is taken for therapeutic purposes remains elusive. Exercise has been shown to create biochemical changes that fertilize the brain environment to improve the health of nerve cells. In addition, exercise induces restorative changes relevant to the pathology of Alzheimer's disease, with improved growth of nerve cells and better connectivity of the hippocampus, a process called hippocampal neurogenesis in adults. For these reasons, the authors Choi et al. examined whether the exercise-induced effects and growth of nerve cells in the hippocampus could be used for therapeutic purposes in Alzheimer's disease to restore brain function.

The researchers found that the memory of animals exercising a murine model of Alzheimer's had significantly increased compared to that of sedentary animals due to an improved neurogenesis of the hippocampus in adults and an increase in the amounts of a specific molecule promoting the growth of brain cells, called BDNF. It is important to note that they may recover brain functions, especially memory, in mice with Alzheimer's disease but without exercise by increasing hippocampal cell growth and BDNF levels by combining genetic (virus injection) and pharmacology. On the other hand, the blockage of hippocampal neurogenesis at the onset of Alzheimer's disease has damaged the health of nerve cells at a later stage, resulting in degeneration of the hippocampus and, subsequently, a Memory. This provides a preclinical proof of concept that a combination of drugs increasing hippocampal neurogenesis in adults and BDNF levels could modify or prevent Alzheimer's disease.

With this work, the amyloid hypothesis does not seem promising, namely that Alzheimer's disease is caused by the deposition of amyloid plaques. In this study, it was shown that the elimination of amyloid plaques was not necessary to improve memory defects, which is consistent with the evidence that plaques can also be found in the brain. Individuals in good health. On the contrary, we could consider a new and improved theory of Alzheimer's disease based on the promotion of a healthier brain environment and hippocampal neurogenesis in adults.

However, this inspiring new must be interpreted with great caution: the mouse models of Alzheimer's disease are renowned for their inability to translate into humans, so that the treatments that have been used to cure mice have failed for humans . In addition, even if these results translate into humans, this may apply to a fraction of Alzheimer's individuals with genetic components relevant to the mouse model used. Future studies will need to replicate these results in murine models mimicking the range of known genetic backgrounds of Alzheimer's disease and, more importantly, proving their medical relevance to human disease.

Before applying these findings to human patients, there is still much research to establish that a drug could mimic the effects of exercise – mimetics – by "cleaning" the brain with BDNF and stimulating neurogenesis to combat Alzheimer's disease. Currently, the method of administering BDNF to laboratory animals – by direct injection into the brain – is not ideal for use in humans, and a compound stimulating the neurogenesis of the brain. The seahorse remains elusive.

Future attempts to develop pharmacological means to mimic and increase the benefits of exercise – exercise mimetics – to increase hippocampal neurogenesis in adults in addition to BDNF may someday be a means to effective in improving cognition in people with Alzheimer's disease. In addition, the increase in neurogenesis during the early stages of the disease may protect neuronal cell death later in the disease, providing a potentially potent treatment strategy modifying the disease.