ArticlePloS one2010
Low-density lipoprotein receptor-related protein 1 (LRP1) mediates neuronal Abeta42 uptake and lysosomal trafficking.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Genetic and environmental risk factors for dementia in African adults: A systematic review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Restores Aβ Clearance by Overcoming PCSK9-LRP1 Dysregulation and TRIB3-Mediated Autophagy Blockade in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modulating LRP1 Pathways in Alzheimer's Disease: Mechanistic Insights and Emerging Therapies.Molecular neurobiology · 2026Review
- Identification of TMED10 as A Regulator for Neuronal Exocytosis of Amyloid Beta 42.Neuroscience bulletin · 2026Article
- Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets.CNS neuroscience & therapeutics · 2025Review
- Endothelial delivery of simvastatin by LRP1-targeted nanoparticles ameliorates pathogenesis of alzheimer's disease in a mouse model.Alzheimer's research & therapy · 2025Article
- Lipidopathy disrupts peripheral and central amyloid clearance in Alzheimer's disease: Where are our knowledge.IBRO neuroscience reports · 2025Review
- APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology.Molecular neurodegeneration · 2025Article
- Amyloid-β oligomers increase the binding and internalization of tau oligomers in human synapses.Acta neuropathologica · 2024Article
- APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology.bioRxiv : the preprint server for biology · 2024Article
- Autophagy-lysosomal pathway impairment and cathepsin dysregulation in Alzheimer's disease.Frontiers in molecular biosciences · 2024Review
- The Potential Therapeutic Application of Simvastatin for Brain Complications and Mechanisms of Action.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies.Molecular neurodegeneration · 2022Review
- Hydroxysafflor Yellow A Inhibits AβNeurochemical research · 2022Article
- Amyloidosis in Alzheimer's Disease: Pathogeny, Etiology, and Related Therapeutic Directions.Molecules (Basel, Switzerland) · 2022Review
- The Relevance of Amyloid β-Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Knockin' on heaven's door: Molecular mechanisms of neuronal tau uptake.Journal of neurochemistry · 2021Review
- The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates.Molecular neurobiology · 2020Article
- Cathepsin D regulates cerebral Aβ42/40 ratios via differential degradation of Aβ42 and Aβ40.Alzheimer's research & therapy · 2020Article
6 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
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlzheimer's disease (AD) is characterized by the presence of early intraneuronal deposits of amyloid-beta 42 (Abeta42) that precede extracellular amyloid deposition in vulnerable brain regions. It has been hypothesized that endosomal/lysosomal dysfunction might be associated with the pathological accumulation of intracellular Abeta42 in the brain. Our previous findings suggest that the LDL receptor-related protein 1 (LRP1), a major receptor for apolipoprotein E, facilitates intraneuronal Abeta42 accumulation in mouse brain. However, direct evidence of neuronal endocytosis of Abeta42 through LRP1 is lacking. METHODOLOGY/PRINCIPAL
findingsHere we show that LRP1 endocytic function is required for neuronal Abeta42 uptake. Overexpression of a functional LRP1 minireceptor, mLRP4, increases Abeta42 uptake and accumulation in neuronal lysosomes. Conversely, knockdown of LRP1 expression significantly decreases neuronal Abeta42 uptake. Disruptions of LRP1 endocytic function by either clathrin knockdown or by removal of its cytoplasmic tail decreased both uptake and accumulation of Abeta42 in neurons. Finally, we show that LRP1-mediated neuronal accumulation of Abeta42 is associated with increased cellular toxicity. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that LRP1 endocytic function plays an important role in the uptake and accumulation of Abeta42 in neuronal lysosomes. These findings emphasize the central function of LRP1 in neuronal Abeta metabolism.
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What OpenQuestion holds
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.