EXPRESSION AND DISTRIBUTION OF LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN MESSENGER-RNA IN THE RAT CENTRAL-NERVOUS-SYSTEM

The low density lipoprotein-receptor-related protein (LRP) is a multif unctional cell surface receptor that binds to the protease inhibitor a lpha-macroglobulin (alpha(2)M). LRP has also been identified as the ap olipoprotein E (apoE) receptor that mediates lipid metabolism. Recentl y it has been reported that apoE4, one of three common isoforms of apo E, is a main risk factor of Alzheimer's disease (AD). Moreover, all th ree of these proteins are reported to accumulate in the senile plaques in the brains of Alzheimer's patients. To understand the roles of LRP in the normal development of the central nervous system (CNS) and in the pathogenesis of AD, we studied the developmental expression and lo calization of LRP mRNA in the CNS. We used Northern blot analysis to i nvestigate the developmental profile of LRP mRNA in the rat brain. LRP mRNA was first detected as early as in 18-day-old embryonic rat brain and was continuously expressed thereafter. A particularly high level of expression of the mRNA was observed in the perinatal stage. We also determined the cellular distribution of LRP mRNA in the CNS of 20-day -old embryonic and 6-week-old adult rat brains by in situ hybridizatio n using a digoxigenin-labeled antisense riboprobe to LRP mRNA. In the embryonic rat brain, LRP mRNA was highly expressed in most of the cell s, mainly neurons and glial cells. In the adult rat, LRP mRNA was expr essed mostly in neurons in both the brain and the spinal cord. These r esults suggest that LRP plays crucial roles in development of the brai n.