ArticleNeuron2021
Overexpressing low-density lipoprotein receptor reduces tau-associated neurodegeneration in relation to apoE-linked mechanisms.
Article in Neuron, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Biomarkers in Ataxia-Telangiectasia: a Systematic Review.Journal of neurology · 2025Pooled it
- Early axonal degeneration linked to clinical decline in Alzheimer's disease progression revealed with diffusion MRI.The Journal of clinical investigation · 2026Trial
- Molecular programs in human locus coeruleus link APOE and neuromelanin to Alzheimer's vulnerability.Acta neuropathologica · 2026Article
- Priming of CD8Nature neuroscience · 2026Article
- ApoE impairs microglial efferocytosis by targeting Gas6/MerTK in a mouse model of acute seizure.Acta pharmacologica Sinica · 2026Article
- Circular RNAEnvironment & health (Washington, D.C.) · 2026Article
- Ferritin-ApoE nanocarrier for targeted therapy of neuromyelitis optica spectrum disorder in mice.Journal of neuroinflammation · 2026Article
- ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer's disease and related disorders.Molecular neurodegeneration · 2026Review
- Protective mutations associated with APOE in Alzheimer's disease.Molecular psychiatry · 2026Review
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Single-nucleus brain transcriptomics reveals microglia dysfunction in multiple system atrophy.Nature communications · 2026Article
- Sex- and age-dependent mitochondrial dysfunction and cognitive impairment in a mouse model of familial hypercholesterolemia.Biology of sex differences · 2026Article
- Alzheimer's disease: from molecular pathways to therapies.Molecular biomedicine · 2026Review
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- CD8bioRxiv : the preprint server for biology · 2026Article
- Cerebrospinal fluid proteomic signatures revealResearch square · 2026Article
- Exploring the toxic mechanism of cypermethrin-induced neurodegeneration diseases via network toxicology and molecular docking.Scientific reports · 2026Article
- Mechanisms, Mediators, and Pharmacological Approaches Targeting Brain Cholesterol Transport in Alzheimer's Disease.Current pharmaceutical design · 2026Review
- Mechanistic role of APOE lipidation in Alzheimer's disease pathogenesis.Theranostics · 2026Review
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
APOE is the strongest genetic risk factor for late-onset Alzheimer's disease. ApoE exacerbates tau-associated neurodegeneration by driving microglial activation. However, how apoE regulates microglial activation and whether targeting apoE is therapeutically beneficial in tauopathy is unclear. Here, we show that overexpressing an apoE metabolic receptor, LDLR (low-density lipoprotein receptor), in P301S tauopathy mice markedly reduces brain apoE and ameliorates tau pathology and neurodegeneration. LDLR overexpression (OX) in microglia cell-autonomously downregulates microglial Apoe expression and is associated with suppressed microglial activation as in apoE-deficient microglia. ApoE deficiency and LDLR OX strongly drive microglial immunometabolism toward enhanced catabolism over anabolism, whereas LDLR-overexpressing microglia also uniquely upregulate specific ion channels and neurotransmitter receptors upon activation. ApoE-deficient and LDLR-overexpressing mice harbor enlarged pools of oligodendrocyte progenitor cells (OPCs) and show greater preservation of myelin integrity under neurodegenerative conditions. They also show less reactive astrocyte activation in the setting of tauopathy.
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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.