A researcher from an investigation led by Case Western Reserve University School of Medicine, has discovered that removing a plaque-forming protein in a mouse model of Alzheimer's disease, can restore one of the earliest known impairments caused by the disease - loss of sense and smell. A summary of the study is published in the Nov. 2 issue of The Journal of Neuroscience.
The investigation verifies that the protein (amyloid beta) is responsible for the loss of sense and smell.
Daniel Wesson, assistant professor of neuroscience at Case Western Reserve and lead investigator, explains:
"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. We can also use smell to see if therapies are working."
Numerous ailments, exposures and injuries can cause loss of smell. Since the 1970's, loss of smell has been identified as an early sign of Alzheimer's. The novel investigation demonstrates the region in the brain and how this happens, and that it can be treated.
Wesson, states: "Understanding smell loss, we think, will hold some clues about how to slow down this disease."
At present there is no effective treatment or cure for Alzheimer's, marked by deteriorating senses, cognition and coordination, eventually leading to death. Currently in the U.S., 5.3 million individuals suffer from the disease, and according to the Alzheimer's Association, this number is predicted to triple to 16 million by 2050.
Wesson collaborated with Anne H. Borkowski, an investigator at the Nathan S. Kline Institute in Orangeburg, N.Y., 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.
The researchers discovered that just a minuscule amount of amyloid beta (too little to be seen on current brain scans) causes mouse models to lose their sense of smell.
They found that the plaque protein gathered initially in parts of the brain linked to smell, long before it started building up in regions connected with cognition and coordination.
Early on, the olfactory bulb, where odor information from the nose is processed, became hyperactive.
However, over time, the level of the protein increased in the olfactory bulb, making it hypoactive (not active enought). Even though the mice spent more time sniffing, they were unable to remember smells and became incapable of telling different odors apart.
The same pattern is observed in individuals with Alzheimer's, as they age they become unresponsive to smells.
Although researchers observed losses in the olfactory system, the rest of the mouse model brain, including the hippocampus, which is the center for memory, continued to act normally in the early stage of Alzheimer's.
"This shows the unique vulnerability of the olfactory system to the pathogenesis of Alzheimer's disease."
The researchers then set out to reverse the effects. They gave the mice a synthetic liver x-receptor agonist, a medication that removes amyloid beta from the brain. After two weeks of treatment on the drug, the mice were able to process smells normally. However, one week after withdrawal of the drug, impairments returned.
Wesson and his team are currently following-up on these findings to find out how amyloid spreads throughout the brain, in order to learn techniques to slow progression of the disease.
Written by Grace Rattue