Journal of Molecular Neuroscience

, Volume 60, Issue 3, pp 325–335 | Cite as

The Complex Role of Apolipoprotein E in Alzheimer’s Disease: an Overview and Update

  • Laura Mahoney-Sanchez
  • Abdel Ali Belaidi
  • Ashley I. Bush
  • Scott AytonEmail author


Apolipoprotein E (ApoE) plays a crucial role in the homeostatic control of lipids in both the periphery and the central nervous system (CNS). In humans, ApoE exists in three different isoforms: ε2, ε3 and ε4. ApoE ε3 is the most common isoform, while the ε4 isoform confers the greatest genetic risk for Alzheimer’s disease (AD). However, the mechanisms underlying how ApoE contributes to the pathogenesis of AD are still debated. ApoE has been shown to impact amyloid β (Aβ) deposition and clearance in the brain. ApoE also has Aβ-independent pathways in AD, which has led to the discovery of new roles of ApoE ranging from mitochondria dysfunction to, most recently, iron metabolism. Here, we review the role of ApoE in health and in AD, with the view of identifying therapeutic approaches that could prevent the risk associated with the ε4 isoform.


Alzheimer’s disease Apolipoprotein E ε4 Neurodegeneration Iron 



The study was supported by Australian National Health and Medical Research Council (NHMRC) and the Australian Research Council (ARC). The Florey Institute of Neuroscience and Mental Health acknowledges support from the Victorian Government, in particular funding from the Operational Infrastructure Support Grant.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.The Florey Institute for Neuroscience and Mental HealthThe University of MelbourneParkvilleAustralia

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