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2005 Grant - Vidal
Biochemical Basis of Phenotypic Variability in Familial Alzheimer's Disease
Ruben Vidal, Ph.D.
Indiana University, Indianapolis
2005 Investigator-Initiated Research Grant
Beta-amyloid is a tiny protein fragment that is a key suspect in Alzheimer's disease pathology. The rare, inherited form of Alzheimer's disease is caused by mutations in one of three genes. All of these genes are involved in the production of beta-amyloid.
Although the link between the mutations and beta-amyloid is fairly well understood, there are many unknowns regarding how these mutations lead to Alzheimer's. For example, researchers have found more than 100 different ways in which just one of the genes may be mutated, suggesting that subsequent outcomes may be more complex than simply affecting beta-amyloid production.
Ruben Vidal, Ph.D., and colleagues are delving into the observation that there are slight variations in beta-amyloid deposits among various cases of familial Alzheimer's disease and that the beta-amyloid deposits in familial Alzheimer's are also slightly different than those in the more common late-onset form of the disease. In this investigation, the researchers will examine the properties of beta-amyloid from brains of people with familial Alzheimer's disease and determine if there is any correlation between variations in these properties and the type of genetic mutation. They will also examine the properties of beta-amyloid from noninherited cases of Alzheimer's.
In related experiments, they will create a catalogue of activated proteins that are associated with each of several Alzheimer-related mutations. This work may indicate whether there is more than one set of molecular events that can contribute to the development of Alzheimer's disease.
This work may lead to a better understanding of the contributing factors in Alzheimer's disease and help researchers improve the genetically modified mice that are often used in studying the disease.