The DOI matches its Crossref record; 175 of the 175 references it cites were found in a registry or an index.
APOE and Alzheimer’s Disease: Evidence Mounts that Targeting APOE4 may Combat Alzheimer’s Pathogenesis
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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“As mentioned above, apoE4 is highly susceptible to neuron-specific proteolysis, which generates neurotoxic fragments [20, 77–79].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [77]
Citations
Cites
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · cited 1×
“Instead, a more violent amyloid model mice known as 5xFAD [50], amyloid plaque deposition was far more in E4FAD mice, and E2/E3FAD mice have considerably higher diffuse plaques with E4FAD showing more dense plaques [51].”
BackgroundApolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69113-7 · Cited by 3,134
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892
Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database
Bertram, L., McQueen, M. B., Mullin, K., Blacker, D., & Tanzi, R. E. (2007) · Nature Genetics · doi:10.1038/ng1934 · Cited by 1,857
Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System
Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W.-H., Castillo, P. E., Shinsky, N., Verdugo, J. M. G., Armanini, M., Ryan, A., et al. (2000) · Neuron · doi:10.1016/s0896-6273(00)80886-7 · Cited by 1,722
Research works printed but not linked: 6
- Sen A, Alkon DL, Nelson TJ (2012) Apolipoprotein E3 (apoE3) but not apoE4 protects against synaptic loss through increased expression of protein kinase Cϵ. J Biol Chem 287(19):15947–15958 · DOI
- Kanekiyo T, Xu H, Bu G (2014) ApoE and Abeta in Alzheimer’s disease: accidental encounters or partners? Neuron 81(4):740–754 · DOI · Paper page
- Cramer PE, Cirrito JR, Wesson DW, Lee CD, Karlo JC, Zinn AE et al (2012) ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. Science 335(6075):1503–1506. · DOI · Paper page
- Riddell DR, Zhou H, Comery TA, Kouranova E, Lo CF, Warwick HK et al (2007) The LXR agonist TO901317 selectively lowers hippocampal Aβ42 and improves memory in the Tg2576 mouse model of Alzheimer’s disease. Mol Cell Neurosci 34(4):621–628. · DOI · Paper page
- Kim J, Jiang H, Park S, Eltorai AE, Stewart FR, Yoon H et al (2011) Haploinsufficiency of human APOE reduces amyloid deposition in a mouse model of amyloid-β amyloidosis. J Neurosci 31(49):18007–18012. · DOI · Paper page
- Kim J, Eltorai AE, Jiang H, Liao F, Verghese PB, Kim J et al (2012) Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis. J Exp Med 209(12):2149–2156. · DOI · Paper page
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Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing
Cunnane, S. C., Trushina, E., Morland, C., Prigione, A., Casadesus, G., Andrews, Z. B., Beal, M. F., Bergersen, L. H., Brinton, R. D., de la Monte, S., et al. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0072-x · Cited by 1,003
Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
Chen, Y., & Yu, Y. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02853-3 · Cited by 516
“ApoE4, the most potent risk factor for the pathogenesis of LOAD, modulates neuroinflammatory response and glial activation [138].”
BackgroundEnergy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 484
Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer's disease
Zaplatić, E., Bule, M. H., Shah, S. Z. A., Uddin, M. S., & Niaz, K. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.03.055 · Cited by 306
Self-citationOxidative stress in alzheimer’s disease: A review on emergent natural polyphenolic therapeutics
Cassidy, L., Fernandez, F., Johnson, J. B., Naiker, M., Owoola, A. G., & Broszczak, D. A. (2019) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2019.102294 · Cited by 288
Metadata
- 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
- Venue
- Molecular Neurobiology
- Published
- 2018-07-21
- Volume
- 56
- Issue
- 4
- Pages
- 2450-2465
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- 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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