Increased levels of apolipoprotein E in the frontal cortex of subjects with schizophrenia

It is unclear whether altered expression of a specific isoform of apolipoprotein E (apoE) is associated with the pathology of schizophrenia. To address whether apoE may be involved in the pathology of schizophrenia, we measured the genotypic and allelic frequency of polymorphisms in its gene and transcriptional regulatory region in DNA from Brodmann’s area (BA) 9 obtained postmortem from schizophrenic and control subjects as well as its levels in the same tissue using Western blot analysis. The genotypic or allelic frequencies of any polymorphism studied did not vary between diagnostic cohorts. There was a significant increase in the levels of apoE protein in BA 9 from the schizophrenic subjects (Mean ± SEM: 270 ± 8.3 vs. 238 ± 7.1 ng apoE/mg protein, p = .008) and a decrease in tissue from an analogous cortical region from rats treated with haloperidol compared with vehicle-treated animals (50 ± 6.4 vs. 116 ± 9.2 ng apoE/mg protein; p = .0002). These data support the hypothesis that increased levels of apoE may be associated with the pathology of schizophrenia and that antipsychotic drugs decrease apoE levels as part of their therapeutic actions.