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2013 Grants - Carulla
Well-Defined Synthetic Mimics for Brain-Derived ABeta Dimers
Natália Carulla, Ph.D.
Institute for Research in Biomedicine
2013 New Investigator Research Grant
Beta-amyloid is a protein fragment at the focus of research into Alzheimer's disease. In some forms, beta-amyloid is toxic to nerve cells and forms clumps of various sizes, eventually forming amyloid plaques, one of the characteristic brain changes associated with Alzheimer's disease. During the last several years, scientists have found extensive evidence that the most toxic forms of beta-amyloid are small clumps known as dimers (containing two beta-amyloid molecules) and oligomers (containing more than two but a small repeated number of beta-amyloid molecules).
To understand how beta-amyloid is toxic to nerve cells, scientists need access to large amounts of dimers and oligomers. At this time, however, these forms of the molecule are difficult to acquire or create. Natàlia Carulla, Ph.D. and colleagues have developed a method to generate beta-amyloid dimers in which the two copies of beta-amyloid are connected by defined chemical bonds. These dimers are designed to mimic those found in the brains of people who have Alzheimer's disease. The researchers plan to study the structures of these dimers, how they form larger clumps, and how they cause nerve cell toxicity. These studies will yield valuable information about the precise structure of beta-amyloid dimers required for toxicity. They may also lead to new ways to detect toxic dimers for use in diagnosing disease and possibly new ways to prevent beta-amyloid toxicity.