Both apolipoprotein E and its receptor, the low‐density‐lipoprotein receptor‐related protein (LRP), are associated with senile plaques in Alzheimer's disease. We examined the relationship of other LRP‐related molecules to senile plaques. LRP is a multifunctional receptor that blinds and rapidly internalizes at least seven ligands: apolipoprotein E, activated α₂‐macroglobulin, tissue and urokinase‐type plasminogen activators, plasminogen activator inhibitor‐1, lipoprotein lipase, and lactoferrin. Using immunohistochemistry, we showed that all of these ligands, representing a diverse group of otherwise apparently unrelated proteins, accumulate on senile plaques. We also studied expression of the receptor‐associated protein, a physiological inhibitor of LRP, in the hippocampal formation from normal subjects and Alzheimer's disease patients. Receptor‐associated protein colocalizes with LRP on neuronal soma, but not on neuronal processes or reactive astrocytes. It is not present on senile plaques. These results suggest that senile plaque‐associated LRP can bind its ligands, but clearance of these compounds may be impaired in the vicinity of senile plaques.