Multiple, diverse senile plaque-associated proteins are ligands of an apolipoprotein E receptor, the alpha 2-macroglobulin receptor/low-density-lipoprotein receptor-related protein.
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 binds and rapidly internalizes at least seven ligands: apolipoprotein E, activated alpha 2-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.
Rebeck
G W
GW
Department of Neurology, Masschusetts General Hospital, Boston 02114.
Harr
S D
SD
Strickland
D K
DK
Hyman
B T
BT
D000544:Alzheimer Disease / Q000473:pathology*; D001057:Apolipoproteins E / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic / Q000032:analysis* / Q000378:metabolism; D011973:Receptors, LDL / Q000032:analysis* / Q000378:metabolism; D012016:Reference Values; D000511:alpha-Macroglobulins / Q000032:analysis* / Q000378:metabolism
D001057:Apolipoproteins E; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D000511:alpha-Macroglobulins