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 situhybridization 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.