Research has shown that the loss of one’s sense of smell can be one of the first warning signs of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. But what are the underlying mechanisms behind this unusual symptom? And is there a common link?
In a new review, researcher Richard L. Doty, Ph.D., a professor of otorhinolaryngology at the Perelman School of Medicine at the University of Pennsylvania and director of the Smell and Taste Center, wanted to find out whether there is a common factor responsible for this loss of smell — one that could also serve as an early warning sign for a number of neurodegenerative diseases.
In the journal Lancet Neurology, Doty cites evidence that the common link could be damage to neurotransmitter and neuromodulator receptors in the forebrain (the front part of the brain).
“We need to retrace the steps of the development of these diseases,” Doty said. “We know loss of smell is an early sign of their onset, so finding common factors associated with the smell loss could provide clues as to the pre-existing processes that initiate the first stages of a number of neurodegenerative diseases.”
“An understanding of such processes could provide novel approaches to their treatment, including ways to slow down or stop their development before irreversible damage has occurred.”
Currently, it is generally believed that this loss of smell is caused by disease-specific pathology. In other words, it is assumed that different diseases can bring about the same loss of smell for different reasons.
Doty’s review, however, looked at many neurodegenerative diseases with varying degrees of smell loss and sought to find a common link that may explain such losses. He considered physiological factors as well as environmental factors like air pollution, viruses, and exposure to pesticides.
“Ultimately, as each possibility was evaluated, there were cases where these factors didn’t show up, which ruled them out as potential universal biomarkers.”
Doty did find compelling evidence for a neurological basis: damage to the neurotransmitter and neuromodulator receptors in the forebrain, particularly when the neurochemical acetylcholine is involved.
Neurotransmitters are the chemicals that send signals throughout the brain, while neuromodulators influence the activity of neurons in the brain. The receptors receive the signals, and if they are damaged, it hurts the brain’s ability to process smells normally.
“The good news is we can assess damage to some of the systems by evaluating their function in living humans using radioactive neurochemicals and brain imaging processes such as positron emission tomography (PET),” Doty said.
“Unfortunately, few data are currently available, and the historical data of damage to neurotransmitter/neuromodulator systems, including cell counts from autopsy studies, are limited to just a few diseases.”
This lack of early data has been a persistent barrier to finding out the origins of smell loss.
“Smell testing isn’t part of a standard check-up, and people don’t recognize a smell problem themselves until it’s already severe,” Doty said. “Research now starting in Japan will be testing thousands of people over the course of the next few years that will better define associations between changes in smell and a wide variety of physiological measures in older populations.”
“If a universal factor does exist, the benefits for patients would be obvious,” Doty said. “Damage to the neurotransmitter and neuromodulator receptors shows promise as one possibility, but we need more research in this area to truly answer the question. It could be the key to unlocking better understanding of neurological disease.”