Cited by 212Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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

Uddin, Md. Sahab, Kabir, Md. Tanvir, Al Mamun, Abdullah, Abdel-Daim, Mohamed M., Barreto, George E., Ashraf, Ghulam Md·2019·Molecular Neurobiology

DOI 10.1007/s12035-018-1237-z

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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.

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Additional file 3 of Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease drug candidate
Nemergut, M., Marques, S. M., Uhrík, L., Váňová, T., Nezvedová, M., Gadara, D. C., Jha, D., Tulis, J., Novakova, V., Planas-Iglesias, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23304976
Additional file 2 of DHCR24 reverses Alzheimer’s disease-related pathology and cognitive impairment via increasing hippocampal cholesterol levels in 5xFAD mice
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Additional file 2 of Efficacy and safety of the novel GlyT1 inhibitor BI 425809 in Alzheimer’s dementia: a randomized controlled trial
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Additional file 1 of Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease drug candidate
Nemergut, M., Marques, S. M., Uhrík, L., Váňová, T., Nezvedová, M., Gadara, D. C., Jha, D., Tulis, J., Novakova, V., Planas-Iglesias, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23304964
Additional file 1 of DHCR24 reverses Alzheimer’s disease-related pathology and cognitive impairment via increasing hippocampal cholesterol levels in 5xFAD mice
Zhang, W.-B., Huang, Y., Guo, X.-R., Zhang, M.-Q., 袁向山, & Zu, H.-B. (2024) · Figshare · doi:10.6084/m9.figshare.26598866

Authors: Uddin, M. S., Kabir, M. T., Al Mamun, A., Abdel-Daim, M. M., Barreto, G. E., & Ashraf, G. M.
Affiliations: Southeast University (BD)
BRAC University (BD)
Pontificia Universidad Javeriana (CO)
King Abdulaziz University (SA)
Corresponding author: Uddin, Md. Sahab
Ashraf, Ghulam Md
ORCID: Uddin, Md. Sahab
Kabir, Md. Tanvir
Barreto, George E.
Ashraf, Ghulam Md
Venue: Molecular Neurobiology
Publisher: Springer Science and Business Media LLC
Published: 2018-07-21
Volume: 56
Issue: 4
Pages: 2450-2465
ISSN: 0893-7648 (ISSN-L)
1559-1182
DOI: 10.1007/s12035-018-1237-z
OpenAlex: W2883974615
Cited by: 212
References: 175
Citations by year: 2026: 9 · 2025: 25 · 2024: 15 · 2023: 34 · 2022: 34 · 2021: 23 · 2020: 49 · 2019: 20 · 2018: 3
FWCI: 3.12
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Molecular Neurobiology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: apolipoprotein E, APOE ε4, Alzheimer's disease, amyloid-beta, tau pathology, APOE isoforms, neuroinflammation, lipid metabolism, synaptic plasticity, synucleinopathies, neurodegeneration
MeSH terms: Alzheimer Disease, Amyloid, Animals, Apolipoproteins E, Humans, Risk Factors, Genetic Predisposition to Disease, Apolipoprotein E4

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

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