Unexpected Link Between Menthol And Alzheimer's Discovered in Mice

A recent study found something strange: When mice with Alzheimer's disease inhale menthol, their cognitive abilities improve.

It seems the chemical compound can stop some of the damage done to the brain that's usually associated with the disease.

In particular, researchers noticed a reduction in the interleukin-1-beta (IL-1β) protein, which helps to regulate the body's inflammatory response – a response that can offer natural protection but one that leads to harm when it's not controlled properly.

The team behind the study, published in April 2023, says it shows the potential for particular smells to be used as therapies for Alzheimer's. If we can figure out which odors cause which brain and immune system responses, we can harness them to improve health.

"We have focussed on the olfactory system's role in the immune and central nervous systems, and we have confirmed that menthol is an immunostimulatory odor in animal models," said immunologist Juan José Lasarte from the Center for Applied Medical Research (CIMA) in Spain when the results were released.

"But, surprisingly, we observed that short exposures to this substance for six months prevented cognitive decline in the mice with Alzheimer's and, what is most interesting, also improved the cognitive ability of healthy young mice."

Having previously observed menthol inhalation boosting the immune response of mice, here the team showed that it could also improve the animals' cognitive abilities, as observed in a series of practical tests in the lab.

In mice with Alzheimer's, the course of menthol for a six-month-long period was enough to stop the cognitive abilities and memory capabilities of the mice from deteriorating. In addition, it appears menthol pushed the IL-1β protein back to safe levels in the brain.

When researchers artificially reduced the number of T regulatory (Treg) cells – known to help keep the immune system in check – some of the same effects were observed, opening a possible route that future treatments could take.

"Both menthol exposure and Treg cell blockade caused a decrease in IL-1β, a protein that could be behind the cognitive decline observed in these models," said neuroscientist Ana Garcia-Osta from CIMA.

"In addition, the specific blockade of this protein with a drug used in treating some autoimmune diseases also improved the cognitive capacity of healthy mice and mice with Alzheimer's."

Scientists have already established numerous links between smells and our immune and nervous systems. These relationships are difficult to fully understand, but we know that our olfactory system can strongly influence the brain. Certain smells may trigger certain responses in the brain, leading to chemical reactions that affect memory, emotion, and more.

Indeed, diseases related to the central nervous system – such as Alzheimer's, Parkinson's, and schizophrenia – often come with a loss of smell. This new research adds some promising data, but plenty more is needed in humans as well as mice.

"This study is an important step toward understanding the connection between the immune system, the central nervous system, and smell," said immunologist Noelia Casares from CIMA.

"The results suggest that odors and immune modulators may play an important role in the prevention and treatment of Alzheimer's and other diseases related to the central nervous system."

The research has been published in Frontiers in Immunology.

An earlier version of this article was published in May 2023.