Apolipoprotein E receptor 2 (apoER2) is a receptor for apolipoprotein E containing lipoprotein and also for Reelin. Apolipoprotein E-associated risk of developing Alzheimer's disease (AD) may be related to its binding to and clearance by cell surface receptors, including members of the low-density lipoprotein receptor family. Otherwise there is circumstantial evidence that the Reelin signaling pathway may contribute to neurodegeneration in AD. To investigate the role of apoER2 on amyloid deposition and neurodegeneration in vivo, we examined the presence of apoER2 in the brains of APP sw transgenic mice (Tg2576) using three apoER2 monoclonal antibodies. Our immunohistochemical study revealed that apoER2 was localized in fine granular structure and reactive astrocytes surrounding amyloid plaques. The double labeling immunohistochemistry revealed that this granular structure overlaps synaptophysin-positive dystrophic neurites. These findings indicate that neuronal apoER2 may play a role for amyloid deposition and neuronal degeneration in AD.