This study is one of the few to characterize immunohistochemically the distribution and localization of Receptor-Associated Protein (RAP) in human autopsy brain. The results show prominent cortical neuronal localization. RAP is clearly identified in large neuronal dendritic/axonal processes. RAP is expressed in both large pyramidal and smaller interneurons. Occasional, much less frequent RAP is detectable in glial cells in white matter, which appear to be predominantly astrocytic. Although RAP is detectable immunohistochemically in Alzheimer's disease autopsy brain, the level of expression appears significantly reduced relative to age-matched control brains. These results suggest, at the immunohistochemical level, that there is a reduction of RAP protein in Alzheimer's disease brain (cortex). In terms of Alzheimer's disease pathophysiology, a reduction of neuronal RAP could then lead to reduced membrane expression of LRP, since RAP has also been shown to be an LRP antagonist.