ArticleThe Journal of biological chemistry2013
A lipoprotein receptor cluster IV mutant preferentially binds amyloid-β and regulates its clearance from the mouse brain.
Article in The Journal of biological chemistry, 2013. 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, 38 citations in OpenAlex.
- Unraveling the Role of LRP1 in Alzheimer's Disease: A Focus on Aβ Clearance and the Liver-Brain Axis.Journal of molecular neuroscience : MN · 2025Pooled it
- Lipidopathy disrupts peripheral and central amyloid clearance in Alzheimer's disease: Where are our knowledge.IBRO neuroscience reports · 2025Review
- Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer's patients: A double-blind placebo-controlled randomized clinical trial.IBRO neuroscience reports · 2024Article
- Anti-malaria drug artesunate prevents development of amyloid-β pathology in mice by upregulating PICALM at the blood-brain barrier.Molecular neurodegeneration · 2023Article
- Microglia and its Genetics in Alzheimer's Disease.Current Alzheimer research · 2021Article
- The Role of Neurovascular System in Neurodegenerative Diseases.Molecular neurobiology · 2020Review
- Is Alzheimer's Disease a Liver Disease of the Brain?Journal of Alzheimer's disease : JAD · 2020Review
- 3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice.The Journal of experimental medicine · 2019Article
- Endothelial LRP1 - A Potential Target for the Treatment of Alzheimer's Disease : Theme: Drug Discovery, Development and Delivery in Alzheimer's Disease Guest Editor: Davide Brambilla.Pharmaceutical research · 2017Review
- Role of LRP1 in the pathogenesis of Alzheimer's disease: evidence from clinical and preclinical studies.Journal of lipid research · 2017Review
- Apolipoprotein E - A Multifunctional Protein with Implications in Various Pathologies as a Result of Its Structural Features.Computational and structural biotechnology journal · 2017Review
- Dissecting the Contribution of Vascular Alterations and Aging to Alzheimer's Disease.Molecular neurobiology · 2016Review
- Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease.Biochimica et biophysica acta · 2016Review
- Amyloid-β Receptors: The Good, the Bad, and the Prion Protein.The Journal of biological chemistry · 2016Review
- ApoE4 upregulates the activity of mitochondria-associated ER membranes.EMBO reports · 2016Article
- Current and future implications of basic and translational research on amyloid-β peptide production and removal pathways.Molecular and cellular neurosciences · 2015Review
- Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer's disease: the role, regulation and restoration of LRP1.Frontiers in aging neuroscience · 2015Review
- Involvement of the Apoer2 and Lrp1 receptors in mediating the pathological effects of ApoE4 in vivo.Current Alzheimer research · 2014Article
- The low-density lipoprotein receptor-related protein 1 and amyloid-β clearance in Alzheimer's disease.Frontiers in aging neuroscience · 2014Review
- The neuropathology of obesity: insights from human disease.Acta neuropathologica · 2014Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Soluble low density lipoprotein receptor-related protein-1 (sLRP1) binds ~70% of amyloid β-peptide (Aβ) in human plasma. In Alzheimer disease (AD) and individuals with mild cognitive impairment converting to AD, plasma sLRP1 levels are reduced and sLRP1 is oxidized, which results in diminished Aβ peripheral binding and higher levels of free Aβ in plasma. Experimental studies have shown that free circulating Aβ re-enters the brain and that sLRP1 and/or its recombinant wild type cluster IV (WT-LRPIV) prevent Aβ from entering the brain. Treatment of Alzheimer APPsw(+/0) mice with WT-LRPIV has been shown to reduce brain Aβ pathology. In addition to Aβ, LRPIV binds multiple ligands. To enhance LRPIV binding for Aβ relative to other LRP1 ligands, we generated a library of LRPIV-derived fragments and full-length LRPIV variants with glycine replacing aspartic acid residues 3394, 3556, and 3674 in the calcium binding sites. Compared with WT-LRPIV, a lead LRPIV-D3674G mutant had 1.6- and 2.7-fold higher binding affinity for Aβ40 and Aβ42 in vitro, respectively, and a lower binding affinity for other LRP1 ligands (e.g. apolipoprotein E2, E3, and E4 (1.3-1.8-fold), tissue plasminogen activator (2.7-fold), matrix metalloproteinase-9 (4.1-fold), and Factor Xa (3.8-fold)). LRPIV-D3674G cleared mouse endogenous brain Aβ40 and Aβ42 25-27% better than WT-LRPIV. A 3-month subcutaneous treatment of APPsw(+/0) mice with LRPIV-D3674G (40 μg/kg/day) reduced Aβ40 and Αβ42 levels in the hippocampus, cortex, and cerebrospinal fluid by 60-80% and improved cerebral blood flow responses and hippocampal function at 9 months of age. Thus, LRPIV-D3674G is an efficient new Aβ clearance therapy.
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Registered trials
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