[Frontiers in Bioscience 16, 962-979, January 1, 2011]

The neurobiology of APOE in schizophrenia and mood disorders

Andrew Stuart Gibbons1,2, Madhara Udawela1,3, Won Je Jeon1, Myoung Suk Seo1,2, Lucy Brooks1,4,5, Brian Dean1,2,6

1Rebecca L Cooper Laboratories, Mental Health Research Institute of Victoria, Parkville, Victoria, Victoria 3052, Australia, 2Department of Psychiatry, The University of Melbourne, Parkville, Victoria 3010, Australia,3The Centre for Neuroscience, The University of Melbourne, Victoria Australia, 4Department of Anatomy and Cell Biology, The University of Melbourne, Parkville, Victoria 3010, Australia, 5Department of Neuroscience, The University of Nottingham, Nottingham, UK, 6Department of Psychological Medicine, Monash University, Clayton, Victoria 3800, Australia

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. APOE and its receptors
3.1. The APOE gene and its allelic variants
3.2. The low density lipoprotein receptor superfamily
4. The role of APOE in central nervous system lipid metabolism
5. The role of APOE in neural function
5.1. Glial signalling and the tripartite synapse
5.2. APOE involvement in synaptic plasticity
5.3. APOE involvement in cognition
6. APOE in schizophrenia
6.1. APOE allelic variation in schizophrenia
6.2. APOE expression in schizophrenia
6.3. Role of APOE in myelin disturbances in schizophrenia\
6.4. APOE receptors in schizophrenia
6.5. Reelin and its receptors in schizophrenia
7. Evidence for APOE abnormalities in major depressive disorder and bipolar disorder
7.1. APOE allelic variation in major depressive disorder and bipolar
7.2. APOE expression in major depressive disorder and bipolar disorder
8. APOE, metabolic disturbances and peripheral drug effects
9. Conclusions and perspectives
10. References

1. ABSTRACT

APOE is a major component of several lipoproteins. In addition to its role as a lipid transport protein APOE also serves a dual role as a glial derived, synaptic signalling molecule and thought to play an important role in synaptic plasticity and cognition. Polymorphisms within the APOE gene have been associated with the incidence of Alzheimer's disease. In light of the similarities in the cognitive deficits experienced in both Alzheimer's disease and schizophrenia as well as the comorbidity of depression in Alzheimer's disease, aberrant APOE signalling has been implicated in the pathologies of schizophrenia and mood disorders. The schizophrenia candidate gene, reelin, also shares common receptors with APOE, further supporting a role for APOE in the pathology of these disorders. This review will summarise the current understanding of the involvement of APOE and its receptors in the symptomatology and pathology of schizophrenia and mood disorders and the implications of this involvement for drug treatment.