Alzheimer’s disease is a progressive neurological disorder that affects millions of people worldwide. Currently, there is no known cure for Alzheimer’s, and available treatments only address the symptoms. However, recent research has shown that activating adult-born neurons could be a promising approach for Alzheimer’s treatment. In this article, we will look at the science behind this theory and explore the potential of activating adult-born neurons as a therapeutic strategy for Alzheimer’s disease.
Researchers at the University of North Carolina at Chapel Hill have discovered a way to potentially treat Alzheimer’s and related dementia by activating new neurons generated through adult hippocampus neurogenesis (AHN). The adult hippocampus neurogenesis generates new neurons in adulthood and has been shown to restore both cognitive and noncognitive functions in mouse models of Alzheimer’s disease. The researchers found that activation of a small population of these new neurons in the supramammillary nucleus (SuM) led to significant behavioral restoration and potential plaque removal, highlighting its potential for future targeted therapies.
Individuals with Alzheimer’s disease experience impairments in cognitive abilities, such as memory, as well as challenges with noncognitive functions, which can result in anxiety and depression. The study published on April 6, 2023 in the journal Cell Stem Cell, examined the process of AHN using mice as subjects. The findings revealed that applying deep brain stimulation to newly formed neurons helped restore both cognitive and noncognitive functions in mouse models of Alzheimer’s disease.
The researchers used optogenetics to stimulate the SuM and enhance AHN in Alzheimer’s mice. Their earlier research had shown that stimulation of the SuM could increase the production of new neurons and improve their qualities in normal adult mice. In the new study, the investigators showed that this strategy was also effective in the Alzheimer’s mice, leading to the generation of new neurons that made better connections with other parts of the brain. However, having more improved new neurons is not enough to improve memory and mood. Behavioral improvement in Alzheimer’s mice was seen only when these improved new neurons were activated by chemogenetics.
To further understand the mechanism, they also analyzed the protein changes in the hippocampus of Alzheimer’s mice in response to activation of SuM-modified adult-born new neurons. They found several well-known protein pathways activated inside cells, including those known to be important for improved memory performance, as well as those that allow clearance of the plaques related to Alzheimer’s.
Juan Song, senior author and associate professor at the University of North Carolina at Chapel Hill, said that the research team is eager to find out the mechanisms that underlie these beneficial effects. Future efforts of the team will focus on developing potential therapeutics that mimic the beneficial effects mediated by activation of SuM-modified new neurons. Ultimately, the hope is to develop first-in-class, highly targeted therapies to treat Alzheimer’s and related dementia. This study was funded by the NIH, Alzheimer’s Association, Brain & Behavior Research Foundation, and the UNC Pharmacology Curriculum predoctoral T32 training grant.
In conclusion, the activation of adult-born neurons shows great promise as a potential treatment for Alzheimer’s disease. It is an exciting area of research that has the potential to lead us towards a better understanding of the disease and how to treat it. By promoting neurogenesis, we may be able to slow the progression of Alzheimer’s disease and improve cognitive function in patients. While there is still much more to be learned, the progress being made in this field is inspiring, and we can remain hopeful that with continued research and development, we will find new and effective treatments for this devastating disease.
