Molecular Insight into the Therapeutic Promise of Targeting APOE4 for Alzheimer's Disease

Oxidative Medicine and Cellular Longevity
Abdullah Al MamunMohamed M Abdel-Daim

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes chronic cognitive dysfunction. Most of the AD cases are late onset, and the apolipoprotein E (APOE) isoform is a key genetic risk factor. The APOE gene has 3 key alleles in humans including APOE2, APOE3, and APOE4. Among them, APOE4 is the most potent genetic risk factor for late-onset AD (LOAD), while APOE2 has a defensive effect. Research data suggest that APOE4 leads to the pathogenesis of AD through various processes such as accelerated beta-amyloid aggregations that raised neurofibrillary tangle formation, cerebrovascular diseases, aggravated neuroinflammation, and synaptic loss. However, the precise mode of actions regarding in what way APOE4 leads to AD pathology remains unclear. Since APOE contributes to several pathological pathways of AD, targeting APOE4 might serve as a promising strategy for the development of novel drugs to combat AD. In this review, we focus on the recent studies about APOE4-targeted therapeutic strategies that have been advanced in animal models and are being prepared for use in humans for the management of AD.

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Citations

Sep 6, 2020·Molecular Neurobiology·Md Tanvir KabirMohamed M Abdel-Daim
Aug 21, 2020·Neurotoxicity Research·Md Sahab UddinGhulam Md Ashraf
Sep 17, 2020·Molecular Neurobiology·Md Sahab UddinMohamed M Abdel-Daim
May 21, 2020·Molecular Neurobiology·Md Sahab UddinGhulam Md Ashraf
Jun 20, 2020·Neurotoxicity Research·Md Tanvir KabirMohamed M Abdel-Daim
Dec 9, 2020·Antioxidants·Judit MarsillachCarlo Cervellati
Jun 20, 2020·Current Topics in Medicinal Chemistry·Md Tanvir KabirMohamed M Abdel-Daim
Feb 23, 2021·Journal of Neuropathology and Experimental Neurology·Jodie B NicholsThomas G Beach
Jun 5, 2020·Current Topics in Medicinal Chemistry·Md Sahab UddinGhulam M Ashraf
Jun 3, 2021·Journal of Personalized Medicine·Stefania ZampattiEmiliano Giardina
Jul 20, 2021·ACS Chemical Neuroscience·Efthalia AngelopoulouChristina Piperi
Aug 1, 2021·Expert Opinion on Drug Discovery·Ramón CacabelosVinogran Naidoo
Nov 25, 2020·Current Gene Therapy·Md Sahab UddinGhulam Md Ashraf

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Methods Mentioned

BETA
immunodepletion
Lipidation
transgenic
antisense oligonucleotides
nuclear translocation

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