Losing the sense of smell, one of the earliest known symptoms Alzheimer's disease, can be revived by removing a plaque-forming protein from the brain, according to the findings of study conducted at Case Western Reserve University School of Medicine that used mice engineered to show features for Alzheimer's disease.

Since the 1970s, loss of the sense of smell has been identified as an early sign of Alzheimer's disease. The new research, published in the November 2 issue of The Journal of Neuroscience, shows how and where in the brain this happens and that the impairment can be treated.

“The evidence indicates we can use the sense of smell to determine if someone may get Alzheimer's disease, and use changes in sense of smell to begin treatments, instead of waiting until someone has issues learning and remembering,” Daniel Wesson, assistant professor of neuroscience at Case Western Reserve and lead investigator said. “We can also use smell to see if therapies are working.”

Protein Formed into Plaque

Wesson worked with Anne H. Borkowski, a researcher at the Nathan S. Kline Institute in Orangeburg, N.Y., BrightFocus grantee Gary E. Landreth, professor of neuroscience at Case Western Reserve School of Medicine and Ralph A. Nixon, Efrat Levy and Donald A. Wilson, of the New York University School of Medicine.

They found that just a tiny amount of the protein—too small to be seen on today's brain scans—causes smell loss in mouse models.

The protein, which is called amyloid beta, forms plaque that accumulated first in parts of the brain associated with smell, well before accumulating in areas associated with cognition and coordination.

Plaque Compromised Smell

Early on, the olfactory bulb, where odor information from the nose is processed, became overactive. Over time, however, the level of amyloid beta increased in the olfactory bulb and the bulb became under active. Despite spending more time sniffing, the mice failed to remember smells and became incapable of telling the difference between odors.

A similar pattern is seen among people with Alzheimer's disease. They become unresponsive to smells as they age. While losses in the olfactory system occurred, the rest of the mouse brain, including the hippocampus, which is a center for memory, continued to act normally early in the disease stage.

“This shows the unique vulnerability of the olfactory system to the pathogenesis of Alzheimer's disease,” Wesson said.

Protein Removal Improved Smell

The team then sought to return the sense of smell. Mice were given a drug that clears amyloid beta from the brain. After two weeks on the drug, the mice could process smells normally.

After withdrawal of the drug for one week, impairments returned.

Wesson and his team are now following-up on these discoveries to determine how amyloid spreads throughout the brain, toward discovering methods to slow Alzheimer's disease progression. 

• Journal of Neuroscience abstract
• Case Western Reserve School of Medicine press release