Massimo Tabaton, M.D.
University of Genoa
Genoa, Italy

2003 Investigator-Initiated Research Grant

The protein fragment beta-amyloid is the prime suspect in Alzheimer’s disease. However, beta-amyloid is a normally occurring protein, also found in the brains of people without the disease. One possible explanation for why beta-amyloid does not always cause Alzheimer’s lies in the fact that the protein fragment exists in several forms that vary slightly in length, and some may be more toxic than others. People whose brains have a higher percentage of more toxic varieties of beta-amyloid may be at higher risk for the disease.

Massimo Tabaton, MD, and colleagues have found that people with rare, inherited forms of early-onset Alzheimer’s disease have beta-amyloid “profiles” that differ from those of people who have the late-onset, nonhereditary form of the disease. In the present study, the researchers will study postmortem brain tissue to investigate whether the beta-amyloid profile of aged people without Alzheimer’s disease differs from those with the disease. If they find differences, the researchers will expose laboratory cultures of brain cells to these profiles to determine the relative toxicities of each. Finally, they will look for these beta-amyloid profile differences in the cerebrospinal fluid of living study participants. If such differences can be found and confirmed in future work, they might serve as tests for diagnosing Alzheimer’s and for assessing the risk of developing the disease.