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2006 Grant - Cattaneo
Recombinant Antibodies Against A-beta Oligomers: In Vivo Targeting and Delivery
Antonino Cattaneo, Ph.D.
European Brain Research Institute
2006 Investigator-Initiated Research Grant
Beta-amyloid protein fragments, key suspects in Alzheimer pathology, assemble themselves into tiny clusters called oligomers, which form larger structures. Subsequent stages of assembly continue, eventually forming a well-characterized feature of Alzheimer's disease, the amyloid plaque.
Recent studies have shown that one or more oligomeric forms of beta-amyloid may be the real culprits of Alzheimer's disease and that these structures may play a key role in disrupting cell-to-cell communication in the brain. Consequently, beta-amyloid oligomers are a target of particular interest for developing diagnostic tools and new therapies.
Antonino Cattaneo, Ph.D., and colleagues are studying a number of specialized antibodies that may function as molecular probes capable of selecting only beta-amyloid oligomers-rather than single beta-amyloid molecules or larger beta-amyloid-based structures. In their experimental system, the antibodies will be delivered to specific cellular compartments in neurons that play a role in sending or receiving messages. This strategy may help them characterize when, where and how oligomers are formed and how they exert a toxic effect.
The researchers will also test the most promising antibody candidates in genetically altered mice that develop an Alzheimer-like disorder. The outcome of this work may answer questions about beta-amyloid's toxic effect and suggest strategies for future drug development studies.