TRANSGENIC MICE OVEREXPRESSING THE NEUROTROPHIC FACTOR S-100-BETA SHOW NEURONAL CYTOSKELETAL AND BEHAVIORAL SIGNS OF ALTERED AGING PROCESSES - IMPLICATIONS FOR ALZHEIMERS-DISEASE AND DOWNS-SYNDROME

S-100 beta is a neurotrophic factor released by astroglial cells and l ocalized to chromosome 21, within the region which is considered oblig ate for Down's syndrome (DS). S-100 beta is increased in the postmorte m brains of both DS and Alzheimer's disease. Transgenic mice, produced by insertion of the human gene for S-100 beta, were examined for dend ritic development at two ages, using an antibody against microtubule a ssociated protein-2 (MAP-2). At the earliest stages, the density of de ndrites within the hippocampus of transgenic animals exceeded that of controls. Also, MAP-2 immunostaining was evident in the region of the cell body. By 1 year of age, the transgenic animals had significant lo ss of dendrites compared to controls and the number of cells showing c ell body staining was further increased. These pathological changes co uld be indicative of the presence of neurofibrillary tangles and cytos keletal collapse. Behaviorally, younger transgenic animals could not p erform in a learning task as well as controls. Together, these finding s suggest that increased S-100 beta in brain may lead to accelerated d evelopment, followed by increased aging. The pathological changes may prove useful as an animal model of Down's syndrome and Alzheimer's dis ease. (C) 1997 Elsevier Science B.V.