The DOI matches its Crossref record; 122 of the 125 references it cites were found in a registry or an index.
Low‐density lipoprotein receptor‐related protein‐1: a serial clearance homeostatic mechanism controlling Alzheimer’s amyloid β‐peptide elimination from the brain
Open accessAbstract
J. Neurochem. (2010) 115 , 1077–1089. Low‐density lipoprotein receptor‐related protein‐1 (LRP1), a member of the low‐density lipoprotein receptor family, has major roles in the cellular transport of cholesterol, endocytosis of 40 structurally diverse ligands, transcytosis of ligands across the blood–brain barrier, and transmembrane and nuclear signaling. Recent evidence indicates that LRP1 regulates brain and systemic clearance of Alzheimer’s disease (AD) amyloid β‐peptide (Aβ). According to the two‐hit vascular hypothesis for AD, vascular damage precedes cerebrovascular and brain Aβ accumulation ( hit 1 ) which then further amplifies neurovascular dysfunction ( hit 2 ) preceding neurodegeneration. In this study, we discuss the roles of LRP1 during the hit 1 and hit 2 stage of AD pathogenesis and describe a three‐level serial LRP1‐dependent homeostatic control of Aβ clearance including (i) cell‐surface LRP1 at the blood–brain barrier and cerebrovascular cells mediating brain‐to‐blood Aβ clearance (ii) circulating LRP1 providing a key endogenous peripheral ‘sink’ activity for plasma Aβ which prevents free Aβ access to the brain, and (iii) LRP1 in the liver mediating systemic Aβ clearance. Pitfalls in experimental Aβ brain clearance measurements with the concurrent use of peptides/proteins such as receptor‐associated protein and aprotinin are also discussed. We suggest that LRP1 has a critical role in AD pathogenesis and is an important therapeutic target in AD.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The brain-to-blood transfer of monomeric Aβ is highly dependent on low-density lipoprotein receptor-related protein 1 (LRP1) [13, 14], which in brain endothelium is primarily located at the abluminal side [13, 15].”
From PCSK9 acts as a key regulator of Aβ clearance across the blood–brain barrier (2022) · cites this paper as [13]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“a key mechanism by which A 𝛃 40 and 42 peptides are cleared from brain-toblood (696).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [696]
The cited source says what the claim attributes to it.
In the citing paper
“The brain-to-blood transfer of monomeric Aβ is highly dependent on low-density lipoprotein receptor-related protein 1 (LRP1) [13, 14], which in brain endothelium is primarily located at the abluminal side [13, 15].”
From PCSK9 acts as a key regulator of Aβ clearance across the blood–brain barrier (2022) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“LRP1 is a key mediator of cerebral Aβ clearance by its rapid Aβ transport across the BBB into the periphery [13, 14].”
From PCSK9 acts as a key regulator of Aβ clearance across the blood–brain barrier (2022) · cites this paper as [13]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · cited 1×
“This in turn leads to a greater accumulation of different Ab species in the brain (Kayed et al. 2003) including neurotoxic Ab oligomers (Walsh et al. 2005; Lesné et al. 2006).”
RetractedThe Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064
Gupta, A., & Uribarri, J. (2016) · Hormone Research in Paediatrics · doi:10.1159/000444053 · Cited by 4,023
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708
Research works printed but not linked: 2
- 10.1172/JCI200113992 · DOI · Paper page
- 10.1016/S0896-6273(04)00533-1 · DOI
Cited by
Sorted by citations
Items 201–262 of 262
Wu, L., Zheng, Q., Guo, Y., Zhang, K., Luo, J., Xiao, S., Li, W., & Yang, M. (2020) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.112783 · Cited by 11
Newman, S. A., Pan, Y., Short, J. L., & Nicolazzo, J. A. (2017) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2017.01.013 · Cited by 11
P-glycoprotein and Alzheimer’s Disease: Threats and Opportunities
Asante, J., & Barger, S. W. (2025) · ASN NEURO · doi:10.1080/17590914.2025.2495632 · Cited by 11
Cao, W., Tian, S., Zhang, H., Zhu, W., An, K., Shi, J., Yuan, Y., & Wang, S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00743 · Cited by 10
Macura, I. J., Milanović, D., Tešić, V., Major, T., Perović, M., Adžić, M., & Ivković, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179400 · Cited by 10
Mazura, A. D., & Pietrzik, C. U. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041268 · Cited by 9
“A central clearance pathway for brain Aβ is the continuous brain-to-blood transport across the BBB, which is highly dependent on cell surface LRP1 activity [90,95,137].”
BackgroundZheng, X., Yuan, W., Li, L., Ma, H., Zhu, M., Li, X., & Feng, X. (2025) · European Journal of Medical Research · doi:10.1186/s40001-025-02937-1 · Cited by 9
Dong, Y., Cao, K., Xiang, J., Qi, X.-L., Xiao, Y., Yu, W., He, Y., Hong, W., & Guan, Z.-Z. (2023) · Neuroscience · doi:10.1016/j.neuroscience.2023.04.023 · Cited by 10
DKK3-LRP1 complex and a chemical inhibitor regulate Aβ clearance in models of Alzheimer’s disease
Yang, R., Wang, L., Li, Y., Zhu, J., Wang, J., Schlessinger, D., & Sima, J. (2025) · Science Advances · doi:10.1126/sciadv.adz2099 · Cited by 8
Roles of Pericytes in the Pathophysiology of Cerebral İschemia
Yemişçi, M., Gürler, G., & Soylu, K. O. (2022) · Nöro Psikiyatri Arşivi · doi:10.29399/npa.28171 · Cited by 8
Gamit, N., Patil, M., Soumya, B. S., Sundaram, S. M., Sethi, G., Dharmarajan, A., & Warrier, S. R. (2023) · Drug Development Research · doi:10.1002/ddr.22102 · Cited by 8
Chiarini, A., Armato, U., Gui, L., Yin, M., Chang, S., & Prà, I. D. (2024) · Brain Research · doi:10.1016/j.brainres.2024.149283 · Cited by 7
Zidan, E. F., El-Mezayen, N. S., El‐Rewini, S. H., Afify, E. A., & Ali, M. A. (2024) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-024-10159-1 · Cited by 7
Signaling Pathways Involved in Cognitive Enhancement
Nelson, T. J., Sun, M., & Alkon, D. L. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-417042-1.00002-4 · Cited by 7
Altered Clearance in Alzheimer's Disease and Cerebral Amyloid Angiopathy
Mohammadi, S., Dolatshahi, M., Rahmani, F., & Raji, C. A. (2025) · Neuroimaging Clinics of North America · doi:10.1016/j.nic.2024.12.004 · Cited by 7
Hou, H., Habib, A., Zi, D., Tian, K., Tian, J., Giunta, B. N., Sawmiller, D. R., & Tan, J. (2017) · NeuroMolecular Medicine · doi:10.1007/s12017-017-8446-x · Cited by 6
Effects of taurine on metal cations, transthyretin and LRP-1 in a rat model of Alzheimer’s disease
Tekin, E., Karakelle, N. A., & Dinçer, S. (2023) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2023.127219 · Cited by 5
Han, S., Lee, S., Kim, J. H., Lee, J., Park, Y. H., Kim, S., Nho, K. T., & Sohn, J. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1411466 · Cited by 5
Riera, M. L., Sáez, A. S., Martín, Á. G., Serrano, M. G., & Minoretti, P. (2024) · Cureus · doi:10.7759/cureus.51650 · Cited by 5
Epidemiology and Clinical Diagnosis
Cohen, R. M. (2013) · PET Clinics · doi:10.1016/j.cpet.2013.08.001 · Cited by 5
Drug Delivery to the Brain Using Endocytic Receptors as Carriers
Talwar, P., Saha, P., Anjana Mohan, A., Divya, S., & Ravanan, P. (2025) · The Receptors · doi:10.1007/978-3-031-81991-9_19 · Cited by 4
Containers Based Drug Delivery for Neuroscience
Jose, D. A., Krishnapriya, & Chakrapani, P. S. B. (2022) · Composites science and technology · doi:10.1007/978-981-16-8146-2_14 · Cited by 4
Syafrita, Y., Amir, D., Susanti, R., & Rasyid, H. E. (2022) · Neurology India · doi:10.4103/0028-3886.344660 · Cited by 4
Soluble LRP-1 in Parkinson’s disease: clues for paradoxical effects
Özdilek, B., & Ağırbaşlı, M. A. (2022) · International Journal of Neuroscience · doi:10.1080/00207454.2022.2131552 · Cited by 4
Treatment and early diagnosis of Parkinson's disease: Opportunities of nanotechnology
Kong, J., Chu, R., Ma, S., & Wang, Y. (2025) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2025.216959 · Cited by 4
Zhao, L., Peng, T., & Wu, S. (2025) · Nanotechnology and nanomaterials. · doi:10.5772/intechopen.1008681 · Cited by 3
Akassoglou, K., Agalliu, D., Chang, C. J., Davalos, D., Grutzendler, J., Hillman, E. M. C., Khakh, B. S., Kleinfeld, D., McGavern, D. B., Nelson, S. J., et al. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00046 · Cited by 3
Aarnio, M., Zhao, P., Yu, S., Christian, C. J., Flanagan‐Steet, H. R., Wells, L., & Steet, R. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.790139 · Cited by 3
Shaping the Future of Chronic Diseases: A Phyto-Mediated Natural Approach
Chougule, P. R. (2025) · Springer eBooks · doi:10.1007/978-3-032-03604-9_15 · Cited by 2
Modulating LRP1 Pathways in Alzheimer’s Disease: Mechanistic Insights and Emerging Therapies
Mushtaq, T., Hameed, H., Khan, M. A., Tariq, U., Hameed, A., & Zaman, M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05775-2 · Cited by 2
ABCA7 rs3764650 Polymorphism is Associated with Delayed Neurocognitive Recovery
Yu, L., Ji, H., Zhou, M., Guo, Y., Liu, J., Lei, D., Han, C., & Ma, T. (2022) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s352810 · Cited by 2
Pepper-Yowell, A. R. (2014) · ThinkTech (Texas Tech University) · Cited by 2
Bhattacharya, I., Bhattacharya, T., Sahu, A., Das, P., Sarkar, S., Prasanna, V. S., Sreed, R., Ravichandiran, V., & Arumugam, S. (2024) · Research Square · doi:10.21203/rs.3.rs-4667019/v1 · Cited by 2
Mechanisms and Clinical Significance of Endosomal Toll-Like Receptors in Neurological Diseases
Kong, W., Miao, X., Dang, R., Jiang, P., & Feng, L. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05364-9 · Cited by 1
Boundary homogenization and numerical modeling of solute transport across the blood-brain barrier
Yousofvand, R., Handy, G., & Tithof, J. (2025) · Physical review. E · doi:10.1103/qr7v-btpp · Cited by 1
Hamdan, A. M. E., Abu‐Elfotuh, K., Alshaman, R., Salem, H. A., Hamdan, A. M., Alaisayi, K. H. A., Alharthi, S. A. S., Aljehani, R. F., Alsharif, F. I. M., Abalhassan, A. K. M., et al. (2026) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2026.110309 · Cited by 1
QKL injection ameliorates Alzheimer's disease-like pathology by regulating expression of RAGE
Dou, J., Zhang, X., Hu, C., Gao, Y., Zhao, Y., Hei, M., Wang, Z., Guo, N., & Zhu, H. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112422 · Cited by 1
Xiong, L., & Wang, Z. (2023) · Neuroscience Letters · doi:10.1016/j.neulet.2023.137159 · Cited by 1
Ahmadpour, D. (2021) · theses.fr (ABES) · doi:10.70675/cf02a85cz66d4z4c79za98czb8e4497ad04c · Cited by 1
Localisation of LRP1 in neurons and glia of the central nervous system
Herbert, R. P. (2014) · UTAS Research Repository · doi:10.25959/23242907
Perman, J. (2011) · Gothenburg University Publications Electronic Archive (Gothenburg University)
Amyloid-β Protofibrils in Alzheimer´s Disease : Focus on Antibodies, Inflammation and Astrocytes
Söllvander, S. (2015) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
석한나 (2014) · YUHSpace (Yonsei University Medical Library)
LRP1 Downregulates the Alzheimer's -Secretase BACE1 by Modulating Its Intraneuronal
Motoki, K., Minegishi, S., Hosaka, A., Mamada, N., Tamaoka, A., Okada, T., Lakshmana, M. K., & Araki, W. (2015)
Peripheral Inflammation and Alzheimer’s Disease: Periodontal Disease
Kamer, A. R., Craig, R. G., & de Leon, M. J. (2016) · Springer eBooks · doi:10.1007/978-3-662-49699-2_8
Microglia and Complement in Alzheimer's Disease with Cerebral Amyloid Angiopathy
Zabel, M. K. (2013) · The Scholars Repository - LLU (Loma Linda University)
Neurochemical Aspects of β-Amyloid Cascade Hypothesis for Alzheimer’s Disease
Farooqui, A. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809937-7.00001-x · Cited by 1
Microfabrication Approaches for Understanding the Role of Vascular Mechanics in Progressive Diseases
Hald, E. S. (2016) · University of Minnesota Digital Conservancy (University of Minnesota)
The Role of Tau in Depression Via the Microtubule Dynamic by Several Regulators: A ReviewPreprint
Wang, H., Yang, C., & Zhu, Z. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4129732
Han, S., Lee, S., Kim, J. H., Lee, J., Park, Y. H., Kim, S., Nho, K. T., & Sohn, J. (2023) · Research Square · doi:10.21203/rs.3.rs-3511390/v1
Chandra, P. K., Selvam, M. K. P., Zulfiquar, T., Rutkai, I., Sikka, S. C., Braun, S. E., Rappaport, J., & Busija, D. W. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02464-w
Raajasekar, S. (2026) · Research Square · doi:10.21203/rs.3.rs-9252110/v1
The Role of LRP1 in Glioma Progression and Therapeutic Targeting: A Narrative Review
Alhujaily, M. M. (2026) · Cells · doi:10.3390/cells15131163
Zhang, M., Huang, X., Yao, L., & Wu, W. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2026.1901256
Zhu, Y.-K., Zhu, Q.-J., Wang, L. F., Hu, H., Wang, X.-J., Zhang, Z.-H., Zhang, W., Tan, L., & Hu, H. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1744647
Tran, M. L., Kim, K., Kim, J. U., Choi, Y. Y., Do, J., Lee, K. H., & Seok, J. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1933036
QCM-D Reveals Parallel Adsorption Pathways Governing Amyloid-β Binding to LRP-1
Lewis, G., Tan, E., Myung, Y., Fan, S., & Johal, M. S. (2026) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6c04707
Metadata
- Authors
- Zlokovic, B. V., Deane, R., Sagare, A. P., Bell, R. D., & Winkler, E. A.
- Affiliations
- University of Rochester Medicine (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2010-10-05
- Volume
- 115
- Issue
- 5
- Pages
- 1077-1089
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC2972355
- OpenAlex
- W1957213374
- Cited by
- 261
- References
- 125
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 19 · 2023: 18 · 2022: 18 · 2021: 11 · 2020: 15 · 2019: 16 · 2018: 7 · 2017: 24 · 2016: 27 · 2015: 17 · 2014: 13 · 2013: 8 · 2012: 25
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R37AG023084)
- National Institute of Neurological Disorders and Stroke (R37NS034467, R01NS034467, R37NS34467)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- LRP1, Alzheimer's disease, blood-brain barrier, hepatic clearance, neurovascular dysfunction, receptor-associated protein, aprotinin, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Brain, Homeostasis, Humans, Amyloid beta-Peptides, LDL-Receptor Related Protein-Associated Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
