ArticleJournal of cell science2021
ApoE4 disrupts interaction of sortilin with fatty acid-binding protein 7 essential to promote lipid signaling.
Article in Journal of cell science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel.Nature metabolism · 2025Article
- A Neural-Glial Model of the ApoE-SORT1-FABP7 Axis Tied to Sleep Disruption and Alzheimer's Disease Pathophysiology.Biomolecules · 2025Review
- Glia-derived noncanonical fatty acid binding protein modulates brain lipid storage and clearance.Science advances · 2025Article
- Genetic Architecture of Ischemic Stroke: Insights from Genome-Wide Association Studies and Beyond.Journal of cardiovascular development and disease · 2025Review
- Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.Molecular neurodegeneration · 2025Review
- Neuronal fatty acid-binding protein enhances autophagy and suppresses amyloid-β pathology in a Drosophila model of Alzheimer's disease.PLoS genetics · 2024Article
- Does glial lipid dysregulation alter sleep in Alzheimer's and Parkinson's disease?Trends in molecular medicine · 2024Review
- Protein intake and episodic memory: the moderating role of the apolipoprotein E ε4 status.Alzheimer's research & therapy · 2024Article
- Sleep and diurnal alternative polyadenylation sites associated with human APA-linked brain disorders.Research square · 2024Article
- Multiple Roles of Apolipoprotein E4 in Oxidative Lipid Metabolism and Ferroptosis During the Pathogenesis of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2024Review
- Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention.Nutrition journal · 2024Article
- FABP7 drives an inflammatory response in human astrocytes and is upregulated in Alzheimer's disease.GeroScience · 2024Article
- Sleep and diurnal alternative polyadenylation sites associated with human APA-linked brain disorders.Npj biological timing and sleep · 2024Article
- Circadian Regulation of Apolipoproteins in the Brain: Implications in Lipid Metabolism and Disease.International journal of molecular sciences · 2023Review
- Roles of ApoE4 on the Pathogenesis in Alzheimer's Disease and the Potential Therapeutic Approaches.Cellular and molecular neurobiology · 2023Review
- The Multifunctional Family of Mammalian Fatty Acid-Binding Proteins.Annual review of nutrition · 2023Review
- FABP7: a glial integrator of sleep, circadian rhythms, plasticity, and metabolic function.Frontiers in systems neuroscience · 2023Article
- Exploring the Role of Lipid-Binding Proteins and Oxidative Stress in Neurodegenerative Disorders: A Focus on the Neuroprotective Effects of Nutraceutical Supplementation and Physical Exercise.Antioxidants (Basel, Switzerland) · 2022Review
- Deciphering Mechanisms of Action of Sortilin/Neurotensin Receptor-3 in the Proliferation Regulation of Colorectal and Other Cancers.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 4 countries.
Funding
Abstract
Sortilin is a neuronal receptor for apolipoprotein E (apoE). Sortilin-dependent uptake of lipidated apoE promotes conversion of polyunsaturated fatty acids (PUFA) into neuromodulators that induce anti-inflammatory gene expression in the brain. This neuroprotective pathway works with the apoE3 variant but is lost with the apoE4 variant, the main risk factor for Alzheimer's disease (AD). Here, we elucidated steps in cellular handling of lipids through sortilin, and why they are disrupted by apoE4. Combining unbiased proteome screens with analyses in mouse models, we uncover interaction of sortilin with fatty acid-binding protein 7 (FABP7), the intracellular carrier for PUFA in the brain. In the presence of apoE3, sortilin promotes functional expression of FABP7 and its ability to elicit lipid-dependent gene transcription. By contrast, apoE4 binding blocks sortilin-mediated sorting, causing catabolism of FABP7 and impairing lipid signaling. Reduced FABP7 levels in the brain of AD patients expressing apoE4 substantiate the relevance of these interactions for neuronal lipid homeostasis. Taken together, we document interaction of sortilin with mediators of extracellular and intracellular lipid transport that provides a mechanistic explanation for loss of a neuroprotective lipid metabolism in AD.
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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.