Zh. Qiu et al., Elevation of LDL receptor-related protein levels via ligand interactions in Alzheimer disease and in vitro, J NE EXP NE, 60(5), 2001, pp. 430-440
Citations number
61
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
The low-density lipoprotein (LDL) receptor-related protein (LRP) is a multi
functional receptor in the CNS that binds both apolipoprotein E (apoE) and
activated alpha2-macroglobulin (alpha 2M*); all 3 proteins are genetically
associated with Alzheimer disease (AD). In this study we found an 85% incre
ase in LRP levels in human AD brain frontal cortex, along with an increased
level of the LRP ligands, apoE. and (alpha 2M. We speculated that LRP leve
ls might be increased in response to the increased levels of its ligands, a
poE, and alpha 2M*. To test this hypothesis we examined the effects of alph
a 2M* on LRP in primary cultures. Treatment of neurons with alpha 2M* signi
ficantly increased LRP levels (by 92%). This increase was prevented by cocu
lture with receptor-associated protein (RAP), which blocks binding of LRP l
igands to LRP. Native alpha 2M or RAP alone did not change LRP levels in vi
tro. We also found that alpha 2M* stimulated activation of astrocytes in vi
tro and promoted the levels of LRP by 65%. These data indicate 1) the LRP l
igand alpha 2M* increases levels of LRP in primary neuronal and astrocytic
cultures, 2) alpha 2M*-induction of LRP levels in vitro depends on binding
to LRP, and 3) LRP levels are increased in AD brain, perhaps in response to
the increased levels of alpha 2M.