Low Density Lipoprotein Receptor-Related Protein and Apolipoprotein E Expression is Altered in Schizophrenia

Abstract

Our recent microarray study reported altered mRNA expression of several low density lipoprotein receptor-related proteins (LRP) associated with the first 4 years following diagnosis with schizophrenia. Whilst this finding is novel, apolipoprotein E (APOE), which mediates its activity through LRPs, has been reported by several studies to be altered in brains of subjects with schizophrenia. We used qPCR to measure the expression of LRP2, LRP4, LRP6, LRP8, LRP10 and LRP12 mRNA in Brodmann's area (BA) 46 of the dorsolateral prefrontal cortex in 15 subjects with short duration of illness schizophrenia (SDS) and 15 pair matched controls. We also used Western blotting to measure APOE protein expression in BA46 from these subjects. Amongst the LRPs examined, LRP10 expression was significantly increased (P = 0.03) and LRP12 was significantly decreased (P < 0.01) in SDS. APOE protein expression was also increased in SDS (P = 0.01). No other marker examined in this study was altered with diagnosis. Our data supports a role for distinct members of the LRP family in the pathology of schizophrenia and adds weight to the hypothesis that aberrant apolipoprotein signaling is involved in the early stages of schizophrenia.

Keywords: Brodmann's area 46; apolipoprotein E; low density lipoprotein receptor-related proteins; prefrontal cortex; schizophrenia.

Figure 1

Western analysis of APOE protein expression in subjects with short duration of illness schizophrenia (SDS) was performed on a 36-kDa immunogenic band, which corresponded to the predicted size of APOE (A). The level of APOE protein expression was increased Brodmann's area 46 from subjects with SDS compared to controls (B). Values are expressed as ratios of APOE expression in an independent BA9 protein extract (internal standard) * P < 0.05.

Figure 2

Levels of (A) LRP10, (B) LRP12, (C) LRP2, (D) LRP4, (E) LRP6 and (F) LRP8 mRNA expression in Brodmann's area 46 from subjects with short duration of illness schizophrenia (SDS) and controls. LRP expression data is expressed as a ratio of the geometric mean of PPIA, SNCA and GAPDH expression. * P < 0.05; ** P < 0.01.