Olfaction, pollution, and Alzheimer's — how are they connected?
Although evidence is mounting, scientists have not yet figured out how airborne particles might impact the brain.
Recently, researchers from Penn State University, PA, investigated possible links between pollution, our sense of smell, and neurological disease.
They published their findings earlier this week in the journal eLife.
To investigate, the researchers were particularly interested in the flow of cerebrospinal fluid (CSF).
CSF is a fluid that surrounds the central nervous system (CNS), which comprises the brain and spinal cord. Classically, it was thought to act as a buffer that protects the CNS, but, over time, scientists have discovered more roles.
Prof. Patrick Drew, one of the authors of the study, explains, "More and more it is realized that it does not just cushion the brain, but may also transfer stuff out of the brain and spinal column area."
The role of CFS in disease
Researchers are growing increasingly interested in the CSF's role in waste clearance, and how it flows around the CNS. To date, researchers are not clear about what manages the production and outflow of CFS.
Neurological conditions, such as Parkinson's and Alzheimer's, are characterized by a buildup of faulty or misshapen proteins; perhaps CSF clearance could play a part.
The scientists wanted to understand how pollution in the air that we breathe influences the CSF and, therefore, refuse collection within the brain; but how would airborne compounds reach the CSF?
Another author of the study, graduate student Jordan N. Norwood, explains his first clue: "I was trying to label cerebrospinal fluid with a dye for another experiment. We started seeing this dyed cerebrospinal fluid drain out through the nose."
Although surprising, Norwood was not the first person to have speculated that CSF might exit the brain through the nose. When he looked through old research papers, there were a few references to this possibility.
The scientists also noted that researchers have already shown that a reduced sense of smell is sometimes an early sign of neurological conditions. For instance, a study published in Neurology concluded that poor performance in an odor identification test might, one day, be a useful way to predict Alzheimer's before the classic symptoms appear.
Destroying sensory nerves
To investigate further, the researchers destroyed the olfactory sensory nerves in mice with zinc sulfate. Interestingly, these nerves are the only part of the mammalian CNS that comes into direct contact with the external environment.
As expected, destroying these sensory nerves removed the mice's ability to smell. Also, it "greatly reduced" the flow of CSF from the nose. The researchers then investigated whether this had any impact on the mice.
According to Prof. Drew, "Animals and people are constantly making CSF, so if it doesn't go out, pressure will go up, but we found that the pressure did not increase after the flow from the nose stopped."
The authors believe that the system must be compensating in other ways; perhaps another pathway is picking up the slack. For instance, the glymphatic system, which is the brain's version of the lymphatic system, might be playing a part.
Alternatively, the body might produce less CSF to avoid increasing pressure within the CNS.
Taking all these findings into consideration, the researchers hypothesize that over time, pollution damages the olfactory sensory neurons. This produces a change in the flow or production of CSF. Because CSF is vital for clearing metabolic trash from the CNS, this plays a part in the development of neurological diseases. The authors write:
"[R]educed CSF turnover may be a contributing factor to the buildup of toxic metabolites and proteins that cause neurodegenerative disorders."
The authors did not set out to prove that this is the exact route by which pollution impacts the brain, but the theory is intriguing. The researchers plan to test their hunch further.
"Next we would like to collaborate with a lab in the Materials Research Institute that is working with soot or jet fuel particles to see if we get the same effect," explains Norwood.
Although these are early days, it will be fascinating to see how this narrative unfolds.