2010 Grants - Levy

Transgenic Models of the Anti-Amyloidogenic Activity of a Mutant Form of ABeta

Efrat Levy, Ph.D.
The Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York

2010 Zenith Fellows Award

Beta-amyloid (also known as Abeta) is a protein fragment that aggregates into amyloid plaques, one of the characteristic features of Alzheimer pathology. Beta amyloid is produced when its precursor, amyloid precursor protein (APP), is cut into smaller pieces.

Efrat Levy, Ph.D. and colleagues have found a mutation of the APP gene that alters how beta amyloid aggregates. When both copies of the gene are mutated, aggregation is enhanced. But when only one copy of the gene is mutated, aggregation is inhibited, presumably because the two different forms of beta amyloid are unable to aggregate together.

Dr. Levy and colleagues have proposed to extend their studies of how mutant APP affects the aggregation of beta amyloid and the development of amyloid plaque. They plan to use mice that have been genetically altered to express various mutant or normal forms of beta amyloid in different combinations. The researchers will first study how different genetic forms of APP affect the production of beta amyloid. They will then focus on how the different genetic forms affect the ability of beta amyloid to form aggregates and cause neurodegeneration. These studies will provide valuable insights into the genetics of amyloid plaque formation, and they may provide clues toward the development of treatments to prevent the aggregation of beta amyloid and subsequent neurodegeneration.