Low density lipoprotein receptor related protein (LRP) is a receptor for protease complexes, and may function in cell growth and repair, and in tumor invasiveness. LRP expression increases in glioblastomas compared to lower grade astrocytomas. Two potential mechanisms for this increased expression were investigated. The LRP C766T polymorphism is protective against Alzheimer's disease, perhaps through alteration of LRP expression. The frequency of the polymorphism was measured in astrocytoma patients and controls, but no significant difference was found. Differential PCR revealed LRP gene amplification in four of 25 high-grade gliomas and 0 of 23 other brain tumors. Co-amplification with epidermal growth factor receptor (EGFR) occurred in all four of the LRP-amplified tumors. Thus, LRP amplification may be partly responsible for increased LRP expression in astrocytomas, and may often occur in conjunction with EGFR amplification.