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Molecular Neurobiology

, Volume 56, Issue 4, pp 2450–2465 | Cite as

APOE and Alzheimer’s Disease: Evidence Mounts that Targeting APOE4 may Combat Alzheimer’s Pathogenesis

  • Md. Sahab UddinEmail author
  • Md. Tanvir Kabir
  • Abdullah Al Mamun
  • Mohamed M. Abdel-Daim
  • George E. Barreto
  • Ghulam Md AshrafEmail author
Article

Abstract

Alzheimer’s disease (AD) is an immutable neurodegenerative disease featured by the two hallmark brain pathologies that are the extracellular amyloid ß (Aß) and intraneuronal tau protein. People carrying the APOE4 allele are at high risk of AD concerning the ones carrying the ε3 allele, while the ε2 allele abates risk. ApoE isoforms exert a central role in controlling the transport of brain lipid, neuronal signaling, mitochondrial function, glucose metabolism, and neuroinflammation. Regardless of widespread indispensable studies, the appropriate function of APOE in AD etiology stays ambiguous. Existing proof recommends that the disparate outcomes of ApoE isoforms on Aβ accretion and clearance have a distinct function in AD pathogenesis. ApoE–lipoproteins combine diverse cell-surface receptors to transport lipids and moreover to lipophilic Aβ peptide, that is believed to begin deadly events that generate neurodegeneration in the AD. ApoE has great influence in tau pathogenesis, tau-mediated neurodegeneration, and neuroinflammation, as well as α-synucleinopathy, lipid metabolism, and synaptic plasticity despite the presence of Aβ pathology. ApoE4 shows the deleterious effect for AD while the lack of ApoE4 is defensive. Therapeutic strategies primarily depend on APOE suggest to lessen the noxious effects of ApoE4 and reestablish the protective aptitudes of ApoE. This appraisal represents the critical interactions of APOE and AD pathology, existing facts on ApoE levels in the central nervous system (CNS), and the credible active stratagems for AD therapy by aiming ApoE. This review also highlighted utmost ApoE targeting therapeutic tactics that are crucial for controlling Alzheimer’s pathogenesis.

Keywords

APOE4 Senile plaques Neurofibrillary tangles Amyloid β Tauopathy Alzheimer’s disease 

Abbreviations

AD

Alzheimer’s disease

Amyloid β

NFTs

Neurofibrillary tangles

ApoE

Apolipoprotein E

Notes

Acknowledgments

The authors are grateful to the Department of Pharmacy, Southeast University, Dhaka, Bangladesh. The authors wish to thank the anonymous reviewer(s)/editor(s) of this article for their constructive reviews.

Authors’ Contributions

This work was carried out in collaboration between all authors. MSU and GMA designed the study, wrote the protocol, and managed the analyses of the study. MSU, MTK, and AAM prepared the first draft of the manuscript. MMA-D, GEB, and GMA revised and improved the first draft. All authors read and approved the final submitted version of the manuscript.

Funding

The authors received no financial support for the research, authorship, and publication of this manuscript.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacySoutheast UniversityDhakaBangladesh
  2. 2.Department of PharmacyBRAC UniversityDhakaBangladesh
  3. 3.Department of PharmacologySuez Canal UniversityIsmailiaEgypt
  4. 4.Department of Ophthalmology and Micro-technologyYokohama City UniversityYokohamaJapan
  5. 5.Departamento de Nutrición y Bioquímica, Facultad de CienciasPontificia Universidad JaverianaBogotá DCColombia
  6. 6.Instituto de Ciencias BiomédicasUniversidad Autónoma de ChileSantiagoChile
  7. 7.King Fahd Medical Research CenterKing Abdulaziz UniversityJeddahSaudi Arabia

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