ArticleJournal of molecular biology2019
The Molecular Basis for Apolipoprotein E4 as the Major Risk Factor for Late-Onset Alzheimer's Disease.
Article in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 55 citations in OpenAlex.
- Inhibition of Moesin and CD44 in stem cell-derived neurons affects the pathological genetic signature associated with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Alzheimer's Disease: From Molecular Pathogenesis to Disease-Modifying Therapies and Clinical Implementation in Aging Populations.Clinical interventions in aging · 2026Review
- Microtubule-associated protein 4 forms aggregates consisting of helical filaments.Biochemistry and biophysics reports · 2025Article
- Serum heat inactivation diminishes ApoE-mediated uptake of D-Lin-MC3-DMA lipid nanoparticles.Beilstein journal of nanotechnology · 2025Article
- Unraveling APOE4's Role in Alzheimer's Disease: Pathologies and Therapeutic Strategies.Current protein & peptide science · 2025Review
- APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Review
- Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer's Disease drug candidate.Molecular neurodegeneration · 2023Article
- Astrocytic APOE4 removal confers cerebrovascular protection despite increased cerebral amyloid angiopathy.Molecular neurodegeneration · 2023Article
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Lipoproteins in the Central Nervous System: From Biology to Pathobiology.Annual review of biochemistry · 2022Review
- In Silico Analysis of the Antagonist Effect of Enoxaparin on the ApoE4-Amyloid-Beta (ABiomolecules · 2022Article
- Natural and Designed Proteins Inspired by Extremotolerant Organisms Can Form Condensates and Attenuate Apoptosis in Human Cells.ACS synthetic biology · 2022Article
- Endogenous Human Proteins Interfering with Amyloid Formation.Biomolecules · 2022Review
- Mechanisms of Transthyretin Inhibition of IAPP Amyloid Formation.Biomolecules · 2021Article
- Review
- Functional insights from biophysical study of TREM2 interactions with apoE and AβAlzheimer's & dementia : the journal of the Alzheimer's Association · 2020Article
- The dark side of Alzheimer's disease: unstructured biology of proteins from the amyloid cascade signaling pathway.Cellular and molecular life sciences : CMLS · 2020Article
- Presence of the apolipoprotein E-ε4 allele is associated with an increased risk of sepsis progression.Scientific reports · 2020Article
- ApoE Lipidation as a Therapeutic Target in Alzheimer's Disease.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Apolipoprotein E4 (ApoE4) is one of three (E2, E3 and E4) human isoforms of an α-helical, 299-amino-acid protein. Homozygosity for the ε4 allele is the major genetic risk factor for developing late-onset Alzheimer's disease (AD). ApoE2, ApoE3 and ApoE4 differ at amino acid positions 112 and 158, and these sequence variations may confer conformational differences that underlie their participation in the risk of developing AD. Here, we compared the shape, oligomerization state, conformation and stability of ApoE isoforms using a range of complementary biophysical methods including small-angle x-ray scattering, analytical ultracentrifugation, circular dichroism, x-ray fiber diffraction and transmission electron microscopy We provide an in-depth and definitive study demonstrating that all three proteins are similar in stability and conformation. However, we show that ApoE4 has a propensity to polymerize to form wavy filaments, which do not share the characteristics of cross-β amyloid fibrils. Moreover, we provide evidence for the inhibition of ApoE4 fibril formation by ApoE3. This study shows that recombinant ApoE isoforms show no significant differences at the structural or conformational level. However, self-assembly of the ApoE4 isoform may play a role in pathogenesis, and these results open opportunities for uncovering new triggers for AD onset.
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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.