A poor sense of smell may be one of the earliest signs of Alzheimer's. Now, researchers have shown that the offending culprit may be beta-amyloid, a protein that builds up in a toxic form in the brains of those with the disease.
Working with laboratory mice that had been bred to develop a disease that resembles Alzheimer's in people, the scientists from Case Western Reserve University School of Medicine showed that removing the plaque-forming protein restores the animals' sense of smell. Researchers believe that the smell centers of the brain may be among the first areas affected by toxic beta-amyloid, followed by brain areas critical for memory and thinking.
“Understanding smell loss, we think, will hold some clues about how to slow down this disease,” said Daniel Wesson, assistant professor of neuroscience at Case Western Reserve and lead investigator for the study, which was published in The Journal of Neuroscience.
Loss of the sense of smell can be caused by many conditions other than Alzheimer’s, including medications, viral illnesses or injuries to the olfactory systems. But a poor sense of smell has also long been recognized as an early sign of Alzheimer's. It may also be an early sign of mild cognitive impairment, a form of memory loss that sometimes precedes Alzheimer's. Not all people with Alzheimer’s lose their sense of smell.
The new research shows how and where in the brain this happens, and that the impairment is likely to be treatable.
Mice exposed to a very minute amount of beta-amyloid lost their ability to detect odors. Plaques made up of the toxic proteins appeared in the rodents' brain areas responsible for smell long before they showed up in areas important for memory. The mice spent more time sniffing than usual but became incapable of remembering smells or telling the differences among odors in lab experiments.
The research team then sought to reverse the effects. The mice were given a drug that clears beta-amyloid 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.
Like the mice in the study, people with Alzheimer's may have a poor sense of smell and be unable to detect common odors like natural gas or roses. But no drugs are currently available that clear beta-amyloid from the brain, though scientists continue to test new candidates.
“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,” Dr. Wesson said. “We can also use smell to see if therapies are working.”
The researchers are continuing their research to determine how beta-amyloid spreads through the brain, and to find new ways to slow its spread and stop the progression of disease.
Source: The Journal of Neuroscience, Nov. 2, 2011. Case Western Reserve Medical School.