ABC transporters function

       Using bioinformatic tools, we have identified 14 ABC transporters that are expressed in the brain. It is apparent that there are no brain-specific ABC transporters: all ABC transporters that have been identified as being expressed in brain are also expressed in at least one other tissue, and several are expressed quite widely. While Table 10.1 provides data about general tissue distribution, further analyses will be required to determine whether these transporters are localized to neurons, glia, or even to cerebral vasculature. The latter point is important, as ABC transporters such as MDR1 and MRP1 represent key elements of the blood-brain barrier and are prominently expressed in cerebrovascular endothelial cells (Cordon- Cardo et al., 1989). We have put forth the hypothesis that ABC transporters are involved in the process of detachment of AP from cellular membranes (Lam et al., 2001).

      A(3 is unlikely to aggregate while attached to the membrane, as the hydrophobic amino acids in the peptide COOH tail would be shielded by their association with the lipid bilayer. On the other hand, the likelihood of Ap aggregation increases substantially following membrane detachment. Thus, detachment of Ap} from the membrane may represent a critical change in the biophysical properties of the peptide, and may very well be a prerequisite to the aggregation events that are thought to be at the core of the pathology of Alzheimer's disease. In summary, we have identified the suite of ABC transporters that are expressed in the brain. Such bioinformatic analysis is a prerequisite to the functional expression of each of these transporters in model systems.

    With such information in hand, we will be able to determine which brainexpressed ABC transporters function as (3-amyloid efflux pumps. Such proteins represent novel targets for the development of drugs that can regulate p-amyloid levels in the brain.