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2012 Grants - Vasilevko
Pyroglutamate Modified Abeta Species in Alzheimer's Disease: Target for Immunotherapy
Vitaly Vasilevko, Ph.D.
University of California, Irvine
2012 New Investigator Research Grant
Beta-amyloid (also known as Abeta) is a protein fragment that aggregates into toxic clusters as well as amyloid plaques, one of the hallmarks of Alzheimer's disease in the brain. Most studies of beta-amyloid have focused on two forms of the molecule, which have 40 or 42 chemical units (amino acids). However, recent studies have identified shorter versions of beta-amyloid that are highly toxic to nerve cells. One of these shorter versions is also modified by the addition of a pyroglutamate chemical group.
Vitaly Vasilevko, Ph.D., and colleagues have performed extensive studies of pyroglutamate-modified beta-amyloid and shown that it is highly toxic and forms aggregates in the brain. Furthermore, its levels in different parts of the brain correspond to levels of neurodegeneration. Dr. Vasilevko's team has proposed to develop a vaccine that directs the immune system to recognize and remove pyroglutamate-modified beta-amyloid from the brain. The researchers will test this vaccine in mice that have been genetically modified to have Alzheimer's-like brain degeneration. This study represents a new approach to the development of vaccines against beta-amyloid, and may be the first step toward the development of a vaccine that can be tested in humans.