ArticleProceedings of the National Academy of Sciences of the United States of America2013
ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 340 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
340 citing papers in PubMed, 556 citations in OpenAlex.
- Neuroproteasomes regulate endogenous tau paired helical filament formation in an APOE genotype- and age-dependent manner.Nature neuroscience · 2026Article
- ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer's disease and related disorders.Molecular neurodegeneration · 2026Review
- Targeting the HDAC4-NHE6-endosomal pH axis restores amyloid-β clearance and cognitive function in Alzheimer's disease mice.Journal of nanobiotechnology · 2026Article
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- Molecular characterization of humanized APOE mouse models reveals source and genotype dependent differences.Molecular neurodegeneration · 2026Article
- APOE-mediated sex differences in microvascular pathology and AD-associated proteinopathies in the medial temporal lobe.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Region-specific brain structural modulation and amyloid-β pathology associated with dietary biotin: insights into dementia neuropathology.EBioMedicine · 2026Article
- Genetic validation of ABI3 p.Ser209Phe variant and its effects on early brain pathology in asymptomatic elderly individuals.Alzheimer's research & therapy · 2026Article
- Article
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Mechanistic role of APOE lipidation in Alzheimer's disease pathogenesis.Theranostics · 2026Review
- Liver-metabolic stress, apolipoprotein E ε4, and cognition and amyloid burden: findings from the dementia platform Korea trial-ready registry.Frontiers in aging neuroscience · 2026Article
- Bioenergetics and lipid metabolism in Alzheimer's disease: From cell biology to systemic health.Journal of internal medicine · 2026Review
- APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer's Disease and Cardiovascular Disease.Molecular neurobiology · 2025Review
- C16-siRNAs in Focus: Development of ALN-APP, a Promising RNAi-Based Therapeutic for Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- APOE isoform-associated tau oligomer polymorphs differ in synaptotoxicity and seeding activity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Alzheimer's Disease: Recent Advances and Controversies.Molecular neurobiology · 2025Review
- DKK3-LRP1 complex and a chemical inhibitor regulate Aβ clearance in models of Alzheimer's disease.Science advances · 2025Article
- Melatonin Supplementation in Alzheimer's disease: The Potential Role in Neurogenesis.Molecular neurobiology · 2025Review
- Disease-disease interactions: molecular links of neurodegenerative diseases with cancer, viral infections, and type 2 diabetes.Translational neurodegeneration · 2025Review
280 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Apolipoprotein E gene (APOE) alleles may shift the onset of Alzheimer's disease (AD) through apoE protein isoforms changing the probability of amyloid-β (Aβ) accumulation. It has been proposed that differential physical interactions of apoE isoforms with soluble Aβ (sAβ) in brain fluids influence the metabolism of Aβ, providing a mechanism to account for how APOE influences AD risk. In contrast, we provide clear evidence that apoE and sAβ interactions occur minimally in solution and in the cerebrospinal fluid of human subjects, producing apoE3 and apoE4 isoforms as assessed by multiple biochemical and analytical techniques. Despite minimal extracellular interactions with sAβ in fluid, we find that apoE isoforms regulate the metabolism of sAβ by astrocytes and in the interstitial fluid of mice that received apoE infusions during brain Aβ microdialysis. We find that a significant portion of apoE and sAβ compete for the low-density lipoprotein receptor-related protein 1 (LRP1)-dependent cellular uptake pathway in astrocytes, providing a mechanism to account for apoE's regulation of sAβ metabolism despite minimal evidence of direct interactions in extracellular fluids. We propose that apoE influences sAβ metabolism not through direct binding to sAβ in solution but through its actions with other interacting receptors/transporters and cell surfaces. These results provide an alternative frame work for the mechanistic explanations on how apoE isoforms influence the risk of AD pathogenesis.
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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.