Inhaling menthol improves cognitive function in Alzheimer's disease

Researchers at Cima University of Navarra have demonstrated in animal models of Alzheimer's disease that inhaling menthol improves cognitive ability. With this study they have discovered that this substance has properties capable of modulating the immune system and that, after a sustained exhibition in time, it can prevent the cognitive deterioration of this neurodegenerative disease. When analyzing its mechanism of action, they observed that smelling this aroma reduced the levels of a protein core topic in mediating the inflammatory response, interleukin-1-beta (IL-1ß). By inhibiting this protein with a drug C for the treatment of some autoimmune diseases, they also managed to improve the cognitive capacity of these sick mice.

This research highlights the potential of odors and immune modulators as therapeutic agents and opens the door to development of therapies based on stimulating and training the olfactory system to prevent or alleviate the effects of Alzheimer's disease and other diseases of the central nervous system. Their results are published in the latest issue of Frontiers in Immnulogy.  

Brain, olfactory and immune system connection

The functional balance of the brain depends on complex interactions between various types of nerve cells, immune cells and neural stem cells. In this complex network of interactions, several programs of study have addressed the immunomodulatory and neurological effects of odorants. Previous work has also shown a correlation between the loss of the sense of smell and the onset of early symptoms in Alzheimer's disease. "We have focused on the role that the olfactory system can play in the immune system and the central nervous system and have confirmed that menthol is an immunostimulant in animal models. But, surprisingly, we observed that exhibition to this substance for six months prevented cognitive decline in Alzheimer's mice and, more interestingly, also improved cognitive ability in healthy young mice," says Dr. Juan José Lasarte, researcher of the Immunology and Immunotherapy Program at Cima and lead author of research.

Another result observed by the researchers is that "blocking a subject of immune cells, the regulatory T cells or Treg, also improved the cognitive ability of the Alzheimer's mouse and caused a clear benefit in the cognitive ability of young healthy mice," explains Dr. Ana Garcia-Osta, a researcher in the Neurological Disease Gene Therapy Program at Cima and co-lead author of this work. "Both exhibition to menthol and blockade of Treg cells caused a decrease in IL-1ß, a protein that could be behind the cognitive impairment observed in these models. Specific blockade of this protein with a drug used in the treatment of some autoimmune diseases also achieved a beneficial effect on cognitive ability in healthy mice and Alzheimer's mice."

"This study is an important step towards understanding the connection between the immune system, the central nervous system and olfaction, as the results suggest that odors and immune modulators may play a relevant role in the prevention and treatment of Alzheimer's and other diseases related to the central nervous system," says Dr. Noelia Casares, also a researcher in the Immunology and Immunotherapy Program and first author of article.

This work has been funded by the Government of Navarra and the Ministry of Economics, Industry and Competitiveness. It is framed within the high school of research Sanitaria de Navarra (IdiSNA). It is also part of project INNOLFACT, a multicenter consortium coordinated by Dr. Enrique Santamaría, researcher of Navarrabiomed. This consortium aims to study olfactory function in aging and to develop new immunomodulatory therapies to slow down the development of neurodegenerative diseases.

reference letter bibliographic

→ Casares Noelia et al. "Improvement of cognitive function in wild-type and Alzheimer's disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells". Frontiers in Immunology. 2023, 14:1130044. doi: 10.3389/fimmu.2023.1130044.