Researchers for the first time have linked the loss of smell with a brain protein associated with Alzheimer's and Parkinson's disease, offering the prospect of a smell test to aid in detecting and tracking illness.
The scientists reported Friday in the journal Brain Research that mice bred to have an excess of the tau protein, a key marker of neurodegenerative diseases, had no interest in new odors, compared with a group of mice with normal levels of the protein.
"The loss of smell has been known for more than a decade as an early sign of several neurodegenerative diseases, but we have never been able to link it to a pathological entity (in the brain) that is measurable over time," said Richard Doty, a professor at the University of Pennsylvania School of Medicine's Smell and Taste Center, and team leader for the study.
Although mental tests and brain imaging scans can give clues, there are currently no physical tests for Alzheimer's disease. There is no cure.
"By tying decreases in the ability to smell to the presence of key disease proteins like tau, we may well be able to assess the degree of progression of selected elements of Alzheimer's disease and related disorders by a patient's score on quantitative smell tests," Dr. Doty said.
In the experiment, which used five normal mice and five genetically engineered as models for Alzheimer's, dysfunction of the sense of smell was rated by measuring the amount of time the mice spent investigating unfamiliar odors such as peppermint. Those with smelling deficits spent little time checking out the new scents.
Analysis of brain tissue from the diseased mice confirmed a link between the loss of smell and the presence of excess tau proteins in brain structures known to be important for smelling. In addition, the genetically engineered mice showed a significant number of tangled nerve connections in the brain, something also connected to Alzheimer's.
Dr. Doty said there is no explanation for why smell perception is affected in people suffering from neurodegenerative diseases, other than that the physical markers of the nerve tangles and amyloid plaques and the signature proteins are found in brain regions associated with perception of odor.
He said his team plans to do more work "to study the progression of the disease entities in the brain as it relates to smell dysfunction. These experiments are part and parcel to better understanding the physical causes of such neurodegenerative diseases."