BRAIN AND ERYTHROCYTE ANION TRANSPORTER PROTEIN, BAND-3, AS A MARKER FOR ALZHEIMERS-DISEASE - STRUCTURAL-CHANGES DETECTED BY ELECTRON-MICROSCOPY, PHOSPHORYLATION, AND ANTIBODIES

Band 3, a ubiquitous membrane transport, regulatory, and structural pr otein, is represented in brain by at least 4 isoforms. Bands 3 in brai n performs the same functions as it does in erythrocytes (RBC). It is susceptible to oxidative damage, which, ultimately, terminates its lif e and that of the cell. We examined the changes band 3 undergoes in Al zheimer's disease (AD) because our previous studies suggest that band 3 is a pivotal protein in neurological disease. Because we hypothesize that AD is a total body disease, we examined peripheral blood cells a s well as brain tissue to determine whether the same changes occur in both. Our results indicate that posttranslational changes occur in RBC band 3 that parallel changes in brain band 3. These include decreased P-32-phosphate labeling in vitro of band 3 polypeptides in brain and RBC, increased degradation of band 3, alterations in band 3 recognized by polyclonal and monoclonal antibodies, and decreased anion and gluc ose transport by blood cells. Serum autoantibodies to band 3 peptides 588-602 and 822-839 were increased in AD patients compared to controls . These band 3 residues lie in anion transport/binding regions. This i s consistent with alteration of this region in AD since it is recogniz ed as antigenically different by the patients' immune system. Our data support an immunological component to AD. The finding that changes in RBC in AD reflect those in brain and can be recognized by antibodies should facilitate development of blood tests for diagnosis and monitor ing, and early therapy. It is anticipated that identification of molec ular sites of posttranslational modification of band 3 will enable us to design specific preventive and treatment strategies, and target dru gs to crucial molecular sites.