Information regarding the genetic factors and environmental conditions that influence presenilin-1 (PS-1) gene expression is essential for the elucidation of its pathophysiological role in Alzheimer's disease (AD). Previous in situ hybridization studies have demonstrated that neurons are the predominant cell type expressing PS-1 in the mammalian central nervous system (CNS) under physiological conditions. In this study, we examined the consequences of an experimentally induced focal injury on PS-1 gene expression in the mouse CNS. Physical lesions to white matter regions produced a robust increase in PS-1 gene expression in non-neuronal cells immediately surrounding the site of injury. These findings underscore the epidemiological evidence that implicate head injury as a risk factor for AD and suggest a possible role for PS-1 in this capacity.