2008 Grants - Wang

Identifying Pathophysiologically Relevant Amyloid-Beta-Degrading Enzyme in Alzheimer's Disease

Dengshun Wang, M.D., Ph.D.
University of Wisconsin-Madison
Madison, Wisconsin

2008 Investigator-Initiated Research Grant

Beta-amyloid (also called amyloid-beta) is a protein fragment found in the brain that aggregates into amyloid plaque, a characteristic feature of Alzheimer pathology. Beta-amyloid is found in the brain even in healthy individuals, but unknown factors cause it to form amyloid plaque in Alzheimer's disease. One possible factor leading to formation of amyloid plaque is the absence or dysfunction of enzymes that normally degrade beta-amyloid.

Recent studies have identified at least three enzymes that degrade beta-amyloid in model systems, but it is not known whether any of these enzymes is altered in Alzheimer's disease. Dengshun Wang, M.D., Ph.D., and colleagues plan to study this question in humans during normal aging, the development of mild cognitive impairment and Alzheimer's disease.

The researchers will take advantage of brain samples collected from individuals who died during participation in a large epidemiologic study of brain degeneration, the Religious Orders Study. They will test these samples for activity of beta-amyloid-degrading enzymes and examine whether loss of enzyme activity is correlated with accumulation of amyloid plaque or the development of cognitive impairment. This study will test an important hypothesis about the cause of Alzheimer's disease and potentially identify targets for the development of treatments for the disease.