Immunostaining of calmodulin and aluminium in Alzheimer's disease-affectedbrains

Previous in vitro studies have shown that Al3+ binds to calmodulin, inducin g alterations in its capability to interact with target proteins, accompani ed by loss of immunological recognition by its conformational specific mono clonal antibody CAM1. In spite of the wealth of data of calmodulin action i n vitro, little information is available on the possible involvement of thi s protein in the pathology typical of Alzheimer's disease. In the present s tudy, we investigated calmodulin immunoreactivity in post-mortem human brai ns affected by Alzheimer's disease, compared with age-matched control brain s. Conformational monoclonal antibodies raised against Ca2+-calmodulin, nam ely CAM1 and CAM4, were used in this study for the characterization of calm odulin. Calmodulin immunorecognition by monoclonal antibody CAM1 was found to be lost in cortical tissue sample from brains affected by Alzheimer's di sease. This finding leads to the hypothesis of a new, possibly inactive, co nformation of the molecule during the disease. On the other hand, CAM4 immu noreactivity was decreased in neurons of brains affected by Alzheimer's dis ease. Anti-Al3+ monoclonal antibodies revealed instead more marked aluminiu m immunoreactivity in the affected brains compared to normal ones. The loss of CAM1 immunoreactivity and the occurrence of large amounts of aluminium suggest an alteration of the active conformation of calmodulin in disease-a ffected brains. These alterations could be involved in the development of A lzheimer's disease pathology. (C) 2001 Elsevier Science Inc.