Abnormal Protein May Explain Loss of Smell With Alzheimer's

The protein kills nerve cells in the nose, animal study finds

URL of this page: http://www.nlm.nih.gov/medlineplus/news/fullstory_117006.html
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By Mary Elizabeth Dallas

Thursday, September 29, 2011 HealthDay Logo

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THURSDAY, Sept. 29 (HealthDay News) -- A loss of a sense of smell can be one of the earliest signs of Alzheimer's disease.

New research suggests that an abnormal form of a protein -- amyloid precursor protein, or APP -- which has been previously associated with the Alzheimer's disease may be to blame.

A study in mice found that animals genetically engineered to produce high levels of the abnormal protein experienced high levels of death in nerve cells in their nose compared to normal mice.

Researchers say the findings may explain why people suffering from the progressive illness often lose their sense of smell while the disease is still in its initial stages. They added this new insight might help doctors detect the condition early on.

"Deficits in odor detection and discrimination are among the earliest symptoms of Alzheimer's disease, suggesting that the sense of smell can potentially serve as a canary in the coal mine for early diagnosis of the disease," study leader Leonardo Belluscio of the U.S. National Institute of Neurological Disorders and Stroke, said in a news release.

"The changes taking place in the olfactory system as a result of Alzheimer's disease may be similar to those in other regions of the brain but appear more rapidly," he added.

APP has been detected in the nose nerve cells of some people with early onset Alzheimer's, a rare form of the disease that runs in families and strikes before age 65.

The researchers found mice making the mutated form of APP had four times as much olfactory nerve cell death at three weeks of age than normal mice.

When researchers blocked the production of high levels of the mutated protein, more olfactory nerve cells survived.

"Reducing APP production suppressed the widespread loss of nerve cells, suggesting that such disease-related death of nerve cells could potentially be stopped," explained Belluscio.

The study, published in the Sept. 28 issue of The Journal of Neuroscience, also found that the cells that died in the nose did not contain amyloid plaques, which are derived from APP. Plaques have long been believed to contribute to the death of nerve cells in the brains of people with Alzheimer's, leading to memory loss.

The researchers say the findings suggest that APP itself may be responsible for the death of nerve cells.
"Together, these results support the hypothesis that amyloid proteins are involved in the degeneration of the brain that occurs with Alzheimer's disease," Donald Wilson of New York University School of Medicine and the Nathan Kline Institute for Psychiatric Research, said in a news release from the journal.

"Further, they provide an exciting opportunity to explore how to prevent or reverse the events that lead to cell death and, ultimately, dementia," added Wilson, an olfactory system expert who was not involved in the study.

While more research is needed, it should be noted that studies involving animals often fail to produce similar results with humans.

SOURCE: Society for Neuroscience, news release, Sept. 27, 2011

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