ApoE and cholesterol in schizophrenia and bipolar disorder: comparison of grey and white matter and relation with APOE genotype

Abstract

47Background: Apolipoprotein E (apoE) and cholesterol play a critical role in synapse and myelin maintenance and integrity and are thus appealing candidates in the pathogenesis of schizophrenia and bipolar disorder. To explore the role of these 2 molecules, we quantified cholesterol and apoE levels in prefrontal grey and white matter in patients with schizophrenia, bipolar disorder and healthy controls. Furthermore, we investigated the relations between apoE and cholesterol levels and the APOE genotype. Methods: We obtained dorsolateral prefrontal grey and white matter from the Stanley Medical Research Institute Brain Collection (schizophrenia n = 35, bipolar disorder n = 35 and controls n = 35). Cholesterol levels were quantified using high-pressure liquid chromatography, whereas apoE was measured by enzyme-linked immunosorbent assay. Results: We found no significant differences in cholesterol or apoE levels among the groups. ApoE levels were higher in grey matter than in white matter in all groups; conversely, levels of cholesterol were higher in white matter than in grey matter. We observed a significant inverse correlation between apoE and cholesterol levels in both grey and white matter. Furthermore, in grey matter, apoE levels were significantly higher in APOE ε2 carriers compared with APOE ε3 or APOE ε4 carriers, with cholesterol levels following the opposite trend. Limitations: Limitations of our study include our inability to control for poten tial confounding variables and the small numbers of APOE ε2 and ε4 carriers in each group. Conclusion: Although large amounts of cholesterol are present in white matter, apoE expression is limited. The APOE genotype may play a role in the regulation of both cholesterol and apoE levels in grey matter. The impact of APOE polymorphisms on lipid homeostasis in people with psychiatric disorders warrants further investigation.

Potential biomarkers in psychiatry: focus on the cholesterol system

“…ApoE has three common potential isoforms, E2, E3 and E4 [54]. It is critical for cholesterol transport and lipoprotein particle metabolism and may also be involved in immune regulation, nerve regeneration, lipolytic enzyme activation, synaptogenesis, may be a ligand for various receptors and may promote neuronal homeostasis as well as tissue repair [53,55]. ApoE is synthesized in most organs and substantial amounts are produced in brain [56], which is the site in the body with the second greatest synthesis [57].…”

“…ApoE-containing lipoproteins bind LDL receptors found in neuronal membranes, acting to signal both axonal growth and neuron survival [59,60]. Both ApoE and cholesterol are essential for maintaining both myelin and neuronal synapses [55]. …”

Association between APOE polymorphisms and lipid profile in Mexican Amerindian population

“…The three ApoE isoforms are originated from the substitution of these amino acid residues and lead to differential functions in lipid metabolism (Boerwinkle, Brown, Sharrett, Heiss, & Patsch, ; Boerwinkle & Utermann, ; Gregg & Brewer, ; Gregg et al, ; Hauser, Narayanaswami, & Ryan, ; Villeneuve, Brisson, & Gaudet, ). Additionally, each isoform of ApoE conveys a different risk of some diseases, such as Alzheimer's disease (AD) (Chen, Baum, Ng, Chan, & Pang, ) schizophrenia (Vila‐Rodriguez, Honer, Innis, Wellington, & Beasley, ), osteoporosis (Singh, Singh, Singh, Juneja, & Kaur, ), or arteriosclerosis, which could be due the different functions and structures of the ApoE isoforms (Mahley, Weisgraber, & Huang, ; Ray, Ahalawat, & Mondal, ).…”

Basic research Apolipoprotein E polymorphism is associated with susceptibility to schizophrenia among Saudis

“…Apolipoprotein E synthesized in astrocytes and oligodendrocytes plays a critical role in growth development and repair of neurons [ 15 , 16 ]. Significantly altered APOE levels in brains of people with schizophrenia have been reported [ 17 – 19 ].…”