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Progression of smell loss offers clues to the treatment of Alzheimer's disease

Date:
April 7, 2011
Source:
NIH/National Institute on Deafness and Other Communication Disorders
Summary:
Loss of smell is a characteristic early symptom among people with Alzheimer's disease, but the relationship between olfactory dysfunction and the progression of the disease is still relatively unknown. New findings propose a pathological mechanism in the olfactory bulb, a small area of the brain above and behind the nose that transmits smell information to other areas of the brain for processing, could play a key role.

Loss of smell is a characteristic early symptom among people with Alzheimer's disease, but the relationship between olfactory dysfunction and the progression of the disease is still relatively unknown.

Daniel Wesson, Ph.D., will be presenting findings based on research funded by the NIDCD and conducted with colleagues at the Nathan S. Kline Institute for Psychiatric Research, the NYU School of Medicine, and Case Western Reserve School of Medicine.

Their findings propose a pathological mechanism in the olfactory bulb, a small area of the brain above and behind the nose that transmits smell information to other areas of the brain for processing, could play a key role. Wesson and his colleagues used a mouse model that overexpresses a human mutation of amyloid precursor protein, a protein involved in making amyloid-beta (Aβ), which is the primary component of the plaques that form in the brains of Alzheimer's patients.

When the mice were 3 months old, the researchers observed Aβ buildup in the olfactory bulb before accumulation in other brain areas and abnormal nervous hyperactivity within the olfactory bulb and the olfactory cortex, which receives input from the olfactory bulb. At 6 months of age, the mice showed impairment in their ability to smell. Later, at 16 months, as olfactory impairment persisted, and Aβ levels increased, the olfactory system became hypoactive.

To directly test whether Aβ caused the dysfunction of olfactory behavior and neural activity, they administered a drug that helps break down Aβ. The drug reduced Aβ plaques by more than 50 percent in the olfactory system and other brain areas and also restored behavioral and neural olfactory function.

Removing one olfactory bulb lowered the amount of Aβ found 6 months later on that side of the brain by more than 50 percent, even in regions that receive no direct olfactory bulb input. This supports a role for early-life olfactory bulb output in the spread of Aβ throughout the brain.

These findings offer three potential applications: a new diagnostic marker that could help doctors diagnose Alzheimer's at earlier stages of the disease; a potential treatment to restore olfactory function in Alzheimer's patients; and a novel pathway for exploring drugs that could, ideally, slow or stop the progression of Alzheimer's disease.

Other collaborators include: Anne H Borkowski, B.S., Gary E Landreth, Ph.D., Efrat Levy, Ph.D., Ralph A Nixon, M.D., Ph.D., and Donald A Wilson, Ph.D.

The platform presentation "Network dysfunction, olfactory behavior impairments, and their reversibility in an Alzheimer's β-amyloidosis mouse model" (#20) takes place Friday, April 15 at the 2011 Annual Meeting of the Association for Chemoreception Sciences (AChemS).


Story Source:

The above story is based on materials provided by NIH/National Institute on Deafness and Other Communication Disorders. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute on Deafness and Other Communication Disorders. "Progression of smell loss offers clues to the treatment of Alzheimer's disease." ScienceDaily. ScienceDaily, 7 April 2011. <www.sciencedaily.com/releases/2011/04/110406192513.htm>.
NIH/National Institute on Deafness and Other Communication Disorders. (2011, April 7). Progression of smell loss offers clues to the treatment of Alzheimer's disease. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2011/04/110406192513.htm
NIH/National Institute on Deafness and Other Communication Disorders. "Progression of smell loss offers clues to the treatment of Alzheimer's disease." ScienceDaily. www.sciencedaily.com/releases/2011/04/110406192513.htm (accessed July 22, 2014).

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