title: The Complex Role of Apolipoprotein E in Alzheimer's Disease: an Overview and Update.
abstract: 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.
authors.affiliation: The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Laura
authors.initials: L
authors.lastname: Mahoney-Sanchez
authors.affiliation: The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Abdel Ali
authors.initials: AA
authors.lastname: Belaidi
authors.affiliation: The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia. scott.ayton@florey.edu.au.
authors.forename: Scott
authors.identifier: http://orcid.org/0000-0002-3479-2427
authors.initials: S
authors.lastname: Ayton
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D020033:Protein Isoforms; D007501:Iron
keywords: Alzheimer’s disease; Apolipoprotein E; Iron; Neurodegeneration; ε4