ReviewNeurobiology of disease2020
Apolipoprotein E and oxidative stress in brain with relevance to Alzheimer's disease.
Review in Neurobiology of disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 180 citations in OpenAlex.
- Hearing loss and dementia: radiologic and biomolecular basis of their shared characteristics. A systematic review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Pooled it
- Apolipoprotein E ε4-dependent associations between carotenoids and cognitive decline: Findings from the MIND (Mediterranean-DASH Intervention for Neurodegenerative delay) randomized controlled trial.The American journal of clinical nutrition · 2025Trial
- Ovarian somatic tissue rejuvenates circulating apolipoproteins and promotes cognitive health in postreproductive female mice.GeroScience · 2026Article
- Oxidative Stress and Its Mitigation in Neurodegenerative Disorders.Antioxidants (Basel, Switzerland) · 2026Article
- Relapse-associated worsening in apolipoprotein E ε4 carriers with relapsing multiple sclerosis.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Systemic immunosuppression limits NK cell therapy efficacy in pancreatic cancer.Molecular cancer · 2026Article
- Alcohol use andAlzheimer's & dementia. Behavior & socioeconomics of aging · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Higher Total Omega-3 PUFA Levels and a Lower Omega-6:Omega-3 Ratio Are Associated with Lower Temporal Lobe Volume in Alzheimer's Disease.Molecular neurobiology · 2026Article
- Article
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- APOE4 impairs Nrf2-PINK1/Parkin-dependent mitochondrial clearance through disrupted antioxidant and mitophagy signaling.Free radical biology & medicine · 2026Article
- Design and synthesis of new phosphazine and triazole derivatives for treatment of Alzheimer's disease: modulating ROS/JNK and Wnt/β-catenin signaling pathways.RSC advances · 2026Article
- Exploratory associations between APOE-εFrontiers in neurology · 2026Article
- Regarding the importance of population diversity validation in Alzheimer's disease models.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Liposomal-Cannabidiol Nanoformulation to Suppress HIV Replication and Reduce Oxidative Stress in Infected Microglia.ACS biomaterials science & engineering · 2025Article
- Hypoxia and Cognitive Functions in Patients Suffering from Cardiac Diseases: A Narrative Review.Journal of clinical medicine · 2025Review
- Pluripotent Cells Expressing APOE4 Exhibit a Pronounced Pro-Apoptotic Phenotype Accompanied by Markers of Hyperinflammation and a Blunted NF-κB Response.International journal of molecular sciences · 2025Article
- Impaired Oxidative Stress Markers and Activities of Matrix Metalloproteinases in Plasma of Patients with Alzheimer's Disease, Emphasizing Sex andInternational journal of molecular sciences · 2025Article
- APOE genotype influences on the brain metabolome of aging mice - role for mitochondrial energetics in mechanisms of resilience in APOE2 genotype.Molecular neurodegeneration · 2025Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Inheritance of apolipoprotein E4 (APOE4) is a major risk factor for development of Alzheimer's disease (AD). This lipoprotein, in contrast to apoE2, has arginine residues at positions 112 and 158 in place of cysteines in the latter isoform. In apoE3, the Cys at residue 158 is replaced by an arginine residue. This differential amino acid composition of the three genotypes of APOE have profound influence on the structure, binding properties, and multiple functions of this lipoprotein. Moreover, AD brain is under a high degree of oxidative stress, including that associated with amyloid β-peptide (Aβ) oligomers. Lipid peroxidation produces the highly reactive and neurotoxic molecule, 4-hydroxynonenal (HNE) that forms covalent bonds with cysteine residues (Cys) [as well as with Lys and His residues]. Covalently modified Cys significantly alter structure and function of modified proteins. HNE bound to Cys residue(s) on apoE2 and apoE3 lessens the chance of HNE damage other proteins. apoE4, lacking Cys residues, is unable to scavenge HNE, permitting this latter neurotoxic molecule to lead to oxidative modification of neuronal proteins and eventual cell death. We posit that this lack of HNE scavenging activity in apoE4 significantly contributes to the association of APOE4 inheritance and increased risk of developing AD. Apoe knock-out mice provide insights into the role of this lipoprotein in oxidative stress. Targeted replacement mice in which the mouse gene of Apoe is separately replaced by the human APOE2, APOE3, or APOE4 genes, while keeping the mouse promoter assures the correct location and amount of the human protein isoform. Human APOE targeted replacement mice have been used to investigate the notion that oxidative damage to and death of neurons in AD and its earlier stages is related to APOE genotype. This current paper reviews the intersection of human APOE genotype, oxidative stress, and diminished function of this lipoprotein as a major contributing risk factor for development of AD. Discussion of potential therapeutic strategies to mitigate against the elevated risk of developing AD with inheritance of the APOE4 allele also is presented.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.