Chronic elevation of S100β protein does not alter APP mRNA expression or promote β-amyloid deposition in the brains of aging transgenic mice

S100β protein, a member of a Ca²⁺-binding protein family present primarily in the nervous system, affects the survival and differentiation of both neurons and glia cells. Elevated levels of S100β protein have been observed in the brains of individuals with Alzheimer Disease (AD), as well as in those with Down Syndrome (DS). We have examined transcript levels from the gene encoding the amyloid precursor protein (APP) in four brain regions of mice from I to 24 months of age. After stable adult levels of expression are reached, APP mRNA levels do not change with aging. APP mRNA levels are independent of normal regional variation in S100β mRNA and protein. Further, chronic exposure to S100 β elevated 2- or 7-fold above normal did not alter the transcript levels of APP in transgenic mice. These results leave open the possibility of focal changes in APP transcription and do not address possible effects of S100β on the complex processing known to occur with APP protein. However, neither control nor transgenic aged mice showed any evidence of abnormal deposition of amyloid in neuritic plaques. These results are discussed in the context of hypotheses about the role of elevated S100β in DS and AD.