S100B is a calcium-binding protein, localized to astroglial cells, which has a variety of neurotrophic functions, including roles in serotonergic neuronal growth, synaptogenesis dendritic branching and apoptosis. In humans, the gene for S100B is found on chromosome 21, within what is considered the obligate region for Down Syndrome (DS) and levels of S100B are increased in brain of both DS and Alzheimer's Disease (AD). We have been characterizing a transgenic mouse overexpressing this protein and have previously found evidence of pathological changes in brains of the mice. In the current study, we have examined the expression of clusterin, a protein expressed in aging neurons, in the mice at two ages. Our findings show increased clusterin expression in the aged S100B mice compared to their CD-1 controls, a finding we have interpreted as further evidence of pathological brain aging.