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2007 Grant - Y. Shen
Elevated BACE1 as a Risk Factor for Progression From MCI to Alzheimer's Disease
Yong Shen, M.D., Ph.D.
Sun Health Research Institute
Sun City, Arizona
Candidate for 2007 Zenith Fellows Award
Beta-amyloid is a protein fragment suspected of disrupting cell-to-cell communication and damaging cells in Alzheimer's disease. The fragment is clipped from a molecule called amyloid precursor protein (APP) in two stages. The first cut is made by a protein called the beta APP cleaving enzyme 1, or BACE1. High levels of beta-amyloid in Alzheimer's disease may be the result of too much BACE1 activity.
Scientists believe that cerebrospinal fluid, which surrounds the brain and spinal cord, may also contain levels of BACE1. Moreover, this fluid may experience changes in BACE1 activity that correspond to BACE1 changes in the aging brain. Thus the detection of BACE1 in cerebrospinal fluid could provide an effective method of diagnosing Alzheimer's disease at an early stage.
In this proposed grant, Yong Shen, M.D., Ph.D., and colleagues will attempt to detect BACE1 activity in samples of human cerebrospinal fluid. They also aim to determine whether such activity becomes altered in people with Alzheimer's, and whether BACE1 activity levels can be used to predict Alzheimer's disease or mild cognitive impairment, a condition that often precedes Alzheimer's. The results of their work could significantly advance the field of Alzheimer diagnosis and might prove helpful in the evaluation of drugs for Alzheimer treatment.