William Mobley, M.D., Ph.D. | Alzheimer's Association

William Mobley, M.D., Ph.D.

University of California, San Diego
San Diego, California
1998 Zenith Fellow

Exploring the Link Between Down Syndrome and Alzheimer's Disease

Dr. William Mobley has received several prestigious research awards from the Alzheimer's Association and nearly $17 million in National Institutes of Health (NIH) funding related to Alzheimer's and other dementias research. He is a leader in the field of Down syndrome research, particularly as it relates to the mechanisms for increased risk of Alzheimer's disease.

Individuals with Down syndrome have a high risk of developing Alzheimer's. By age 40, the majority of people with Down syndrome show brain changes associated with Alzheimer's, including the build-up of beta-amyloid plaques and tau neurofibrillary tangles. People with Down syndrome have an extra copy of chromosome 21, which houses the gene that codes for amyloid precursor protein (APP). APP is the parent protein of beta-amyloid, a protein fragment that accumulates into amyloid plaques, a key feature of Alzheimer's disease.

Dr. Mobley's research has shed new light on how high levels of APP associated with Down syndrome may contribute to the development of Alzheimer's. He has shown that APP can both increase the build-up of beta-amyloid and hinder a protein called nerve growth factor (NGF) that is needed for the health and survival of neurons. Specifically, Dr. Mobley and his team have shown that APP impedes the functions of cellular structures called endosomes, which transport NGF to needed locations in the neurons. Endosome dysfunction is known to occur early in the Alzheimer's disease, and these findings are helping scientists dig down to the level of detail needed to develop targeted treatments. Dr. Mobley is currently using mouse models of Down syndrome to determine if a novel drug that modulates the processing of APP can prevent nerve cell damage and preserve cognitive function. In addition, researchers at the UCSD Down Syndrome Center for Research and Treatment, in collaboration with the biotech company AC Immune, are currently conducting the first clinical trial of a vaccine against beta-amyloid in individuals with Down syndrome. The vaccine works by stimulating the immune system to produce antibodies that are designed to bind to and remove toxic beta-amyloid from the brain. The vaccine is also being tested in people with Alzheimer's disease, which shows how important it is for these two communities to work together.

Dr. Mobley's commitment to unraveling the fundamental mechanisms that may underlie Alzheimer's in people with Down syndrome has also advanced our knowledge of the potential causes of familial and sporadic Alzheimer's. It is the hope that these common mechanisms can be successfully targeted to develop new treatments for all people with Alzheimer's disease.

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