INCREASED LEVELS OF HEMOGLOBIN-DERIVED AND OTHER PEPTIDES IN ALZHEIMERS-DISEASE CEREBELLUM

Several studies point to the importance of peptides and proteolysis in Alzheimer's disease (AD). Because of its ability to study small prote ins and peptides, reverse-phase HPLC was employed to study these speci es in AD. Cerebellum was chosen for these initial studies because it d oes not show significant neuronal loss but does show some pathology in AD. Examination of over 600 peptide peaks per case revealed 15 that w ere elevated in AD. Nine were fragments of hemoglobin, and the remaind er included two species of calmodulin, two of myelin basic protein, an d one each of 67 kDa neurofilament protein and PEP-19. The cleavage si tes on hemoglobin were after hydrophobic residues and immunolocalizati on was seen preferentially around blood vessel walls and granule cells . The elevation of the non-serum-derived peptides was characteristic o f general metabolic changes that occurred in AD cerebellum, and the pr esence of elevated hemoglobin polypeptides indicated either possible d isruption of the blood-brain barrier or selective evasion of it by pep tidaceous products. Further studies are required to establish whether hemoglobin fragments have a role in neurodegenerative processes such a s AD.