APOE ε4: The most prevalent yet understudied risk factor for Alzheimer's disease |
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| Institution: | 1. Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands;2. Neuroimaging Department, CITA-Alzheimer Foundation, San Sebastian, Spain;3. Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands;4. Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain;5. Donostia Unit, Osatek SA, Donostia Univeristy Hospital, San Sebastian, Spain;6. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands;1. Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), Rua Botucatu 740, Vila Clementino, CEP 04023-900 São Paulo, SP, Brazil;2. Department of Morphology and Genetics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil;1. Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA;2. Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, College of Medicine, Xiamen University, Xiamen 361005, China;1. Taub Institute for Research on Alzheimer''s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA;2. G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA;3. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA;4. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA;5. Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA;6. Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA;7. Inserm, 1061 Neuropsychiatry, La Colombière Hospital, Montpellier, France;8. Faculty of Medicine University of Montpellier 1, Montpellier, France;9. Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College, University College London, London, UK |
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| Abstract: | Brain pathology of Alzheimer's diseases (AD) and the genetics of autosomal dominant familial AD have been the “lamp posts” under which the AD field has been looking for therapeutic targets. Although this approach still remains valid, none of the compounds tested to date have produced clinically meaningful results. This calls for developing complementary therapeutic approaches and AD targets. The allele ε4 of apolipoprotein E4 (APOE ε4), is the most prevalent genetic risk factor for sporadic AD, and is expressed in more than half of the AD patients. However, in spite of its genetic prominence, the allele APOE ε4 and its corresponding protein product apoE4 have been understudied. We presently briefly discuss the reasons underlying this situation and review newly developed AD therapeutic approaches that target apoE4 and which pave the way for future studies. |
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| Keywords: | Alzheimer's disease ApoE4 Therapy Immunotherapy Lipidation |
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