The DOI matches its Crossref record; 96 of the 96 references it cites were found in a registry or an index.
Physiological blood–brain transport is impaired with age by a shift in transcytosis
Open accessAbstract
The vascular interface of the brain, known as the blood-brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability 1-3. Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins 4,5. Thus, it is unclear whether permeability to individually injected exogenous tracers-as is standard in BBB studies-fully represents blood-to-brain transport. Here we label hundreds of proteins constituting the mouse blood plasma proteome, and upon their systemic administration, study the BBB with its physiological ligand. We find that plasma proteins readily permeate the healthy brain parenchyma, with transport maintained by BBB-specific transcriptional programmes. Unlike IgG antibody, plasma protein uptake diminishes in the aged brain, driven by an age-related shift in transport from ligand-specific receptor-mediated to non-specific caveolar transcytosis. This age-related shift occurs alongside a specific loss of pericyte coverage. Pharmacological inhibition of the age-upregulated phosphatase ALPL, a predicted negative regulator of transport, enhances brain uptake of therapeutically relevant transferrin, transferrin receptor antibody and plasma. These findings reveal the extent of physiological protein transcytosis to the healthy brain, a mechanism of widespread BBB dysfunction with age and a strategy for enhanced drug delivery.
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 cited source says what the claim attributes to it.
In the citing paper
“To determine the samples size for the single-cell sequencing studies, we used previous studies13,26 and performed preliminary studies to confirm that we will obtain enough BECs for statistical analysis (not included in the manuscript).”
From Exercise plasma boosts memory and dampens brain inflammation via clusterin (2021) · cites this paper as [26]
In the citing paper
“BBB permeability becomes less selective with aging because of a loss of tight junctions and a shift from tightly regulated receptor-mediated transcytosis toward nonspecific transcytosis of plasma proteins (136, 137).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [137]
In the citing paper
“In parallel, the entry of inflammatory cytokines and chemokines occurs through active transport or nonspecific caveolar transcytosis (137, 142).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [137]
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
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206
Tissue-based map of the human proteome
Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, Å., Kampf, C., Sjöstedt, E., Asplund, A., et al. (2015) · Science · doi:10.1126/science.1260419 · Cited by 15,286
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174
Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., Benveniste, H., Vates, G. E., Deane, R., Goldman, S. A., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003748 · Cited by 5,824
The MaxQuant computational platform for mass spectrometry-based shotgun proteomics
Tyanova, S., Temu, T., & Cox, J. (2016) · Nature Protocols · doi:10.1038/nprot.2016.136 · Cited by 4,858
The Gene Ontology (GO) database and informatics resource
Gene Ontology Consortium (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh036 · Cited by 4,596
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137
GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
Eden, E., Navon, R., Steinfeld, I., Lipson, D., & Yakhini, Z. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-48 · Cited by 3,356
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
Cited by
Sorted by citations
Wilson, J. E., Mart, M. F., Cunningham, C. M., Shehabi, Y., Girard, T. D., MacLullich, A. M. J., Slooter, A. J. C., & Ely, E. W. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-00223-4 · Cited by 1,371
Strategies for delivering therapeutics across the blood–brain barrier
Terstappen, G. C., Meyer, A. H., Bell, R. D., & Zhang, W. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00139-y · Cited by 1,138
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Agam, M., Maat, C. A., Losada, P. M., Chen, M. B., Schaum, N., Khoury, N., et al. (2022) · Nature · doi:10.1038/s41586-021-04369-3 · Cited by 797
Self-citationThe blood–brain barrier in systemic infection and inflammation
Galea, I. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00757-x · Cited by 807
The blood-brain barrier in aging and neurodegeneration
Knox, E. G., Aburto, M. R., Clarke, G., Cryan, J. F., & O’Driscoll, C. M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01511-z · Cited by 738
“There is an age-related shift in transport from receptor-mediated transport to caveolar transcytosis which may account for some of these changes mentioned, namely an increase in IgG antibody, but a decrease in plasma protein uptake [54].”
BackgroundInfluentialDysregulation of brain and choroid plexus cell types in severe COVID-19
Yang, A. C., Kern, F., Losada, P. M., Agam, M. R., Maat, C. A., Schmartz, G. P., Fehlmann, T., Stein, J. A., Schaum, N., Lee, D. P., et al. (2021) · Nature · doi:10.1038/s41586-021-03710-0 · Cited by 620
Self-citationRasmussen, M. K., Mestre, H., & Nedergaard, M. (2021) · Physiological Reviews · doi:10.1152/physrev.00031.2020 · Cited by 642
Parker, K. R., Migliorini, D., Perkey, E., Yost, K. E., Bhaduri, A., Bagga, P., Haris, M., Wilson, N. E., Liu, F., Gabunia, K., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.022 · Cited by 464
Exercise plasma boosts memory and dampens brain inflammation via clusterin
De Miguel, Z., Khoury, N., Betley, M. J., Lehallier, B., Willoughby, D., Olsson, N., Yang, A. C., Hahn, O., Lu, N., Vest, R. T., et al. (2021) · Nature · doi:10.1038/s41586-021-04183-x · Cited by 422
Self-citationDrug delivery to the central nervous system
Nance, E. A., Pun, S. H., Saigal, R., & Sellers, D. L. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00394-w · Cited by 442
Aburto, M. R., & Cryan, J. F. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00890-0 · Cited by 407
Healthy aging and the blood–brain barrier
Banks, W. A., Reed, M. J., Logsdon, A. F., Rhea, E. M., & Erickson, M. A. (2021) · Nature Aging · doi:10.1038/s43587-021-00043-5 · Cited by 319
Propson, N. E., Roy, E. R., Litvinchuk, A., Köhl, J., & Zheng, H. (2021) · Journal of Clinical Investigation · doi:10.1172/jci140966 · Cited by 258
Platelet factors attenuate inflammation and rescue cognition in ageing
Schroer, A. B., Ventura, P. B., Sucharov, J., Misra, R., Chui, M. K. K., Bieri, G., Horowitz, A. M., Smith, L. K., Encabo, K., Tenggara, I., et al. (2023) · Nature · doi:10.1038/s41586-023-06436-3 · Cited by 252
Zou, Y., Sun, X., Yang, Q., Zheng, M., Shimoni, O., Ruan, W., Wang, Y., Zhang, D., Yin, J., Huang, X., et al. (2022) · Science Advances · doi:10.1126/sciadv.abm8011 · Cited by 227
Zhou, X., Smith, Q. R., & Liu, X. (2021) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1695 · Cited by 229
Atlas of the aging mouse brain reveals white matter as vulnerable foci
Hahn, O., Foltz, A. G., Atkins, M., Kedir, B., Moran-Losada, P., Guldner, I. H., Munson, C., Kern, F., Pálovics, R., Lu, N., et al. (2023) · Cell · doi:10.1016/j.cell.2023.07.027 · Cited by 213
Self-citationBlood–Brain Barrier Breakdown in Alzheimer’s Disease: Mechanisms and Targeted Strategies
Alkhalifa, A. E., Al-Ghraiybah, N. F., Odum, J., Shunnarah, J. G., Austin, N., & Kaddoumi, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216288 · Cited by 212
Vagus nerve stimulation in brain diseases: Therapeutic applications and biological mechanisms
Wang, Y., Zhan, G., Cai, Z., Jiao, B., Zhao, Y., Li, S., & Luo, A. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.04.018 · Cited by 211
APOE4 derived from astrocytes leads to blood–brain barrier impairment
Jackson, R. J., Meltzer, J. C., Nguyen, H., Commins, C., Bennett, R. E., Hudry, E., & Hyman, B. T. (2022) · Brain · doi:10.1093/brain/awab478 · Cited by 205
Tumor Abnormality-Oriented Nanomedicine Design
Zhou, Q., Xiang, J., Qiu, N., Wang, Y., Piao, Y., Shao, S., Tang, J., Zhou, Z., & Shen, Y. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00062 · Cited by 203
Connecting aging biology and inflammation in the omics era
Walker, K. A., Basisty, N., Wilson, D. M., & Ferrucci, L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158448 · Cited by 189
Single-cell atlas of the human brain vasculature across development, adulthood and disease
Wälchli, T., Ghobrial, M., Schwab, M., Takada, S., Zhong, H., Suntharalingham, S., Vetiska, S., Rodríguez, D. G., Wu, R., Rehrauer, H., et al. (2024) · Nature · doi:10.1038/s41586-024-07493-y · Cited by 217
Neurovascular coupling: motive unknown
Drew, P. J. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.08.004 · Cited by 179
Blood-to-brain communication in aging and rejuvenation
Bieri, G., Schroer, A. B., & Villeda, S. A. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01238-8 · Cited by 156
Glycocalyx dysregulation impairs blood–brain barrier in ageing and disease
Shi, S. M., Suh, R. J., Shon, D. J., García, F., Buff, J. K., Atkins, M., Li, L., Lu, N., Sun, B., Luo, J., et al. (2025) · Nature · doi:10.1038/s41586-025-08589-9 · Cited by 164
Self-citationPrecision drug delivery to the central nervous system using engineered nanoparticles
Gao, J., Xia, Z. J., Gunasekar, S., Jiang, C., Karp, J. M., & Joshi, N. (2024) · Nature Reviews Materials · doi:10.1038/s41578-024-00695-w · Cited by 173
Non-Invasive Drug Delivery across the Blood–Brain Barrier: A Prospective Analysis
Niazi, S. K. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15112599 · Cited by 155
Mechanisms of NLRP3 priming in inflammaging and age related diseases
Gritsenko, A., Green, J., Brough, D., & López‐Castejón, G. (2020) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2020.08.003 · Cited by 146
The barrier and interface mechanisms of the brain barrier, and brain drug delivery
Zhang, S., Gan, L., Cao, F., Wang, H., Gong, P., Ma, C., Ren, L., Lin, Y., & Lin, X. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.09.017 · Cited by 129
The neurovascular unit and systemic biology in stroke — implications for translation and treatment
Tiedt, S., Buchan, A. M., Dichgans, M., Lizasoaín, I., Moro, M. Á., & Lo, E. H. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00703-z · Cited by 135
Park, C., Hahn, O., Gupta, S. K., Moreno, A. J., Marino, F., Kedir, B., Wang, D., Villeda, S., Wyss‐Coray, T., & Dubal, D. B. (2023) · Nature Aging · doi:10.1038/s43587-023-00468-0 · Cited by 133
Self-citationDefining blood-induced microglia functions in neurodegeneration through multiomic profiling
Mendiola, A. S., Yan, Z., Dixit, K., Johnson, J. R., Bouhaddou, M., Meyer-Franke, A., Shin, M.-G., Yong, Y., Agrawal, A., MacDonald, E., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01522-0 · Cited by 124
Kucharz, K., Kristensen, K., Johnsen, K. B., Lund, M. A., Lønstrup, M., Moos, T., Andresen, T. L., & Lauritzen, M. J. (2021) · Nature Communications · doi:10.1038/s41467-021-24323-1 · Cited by 123
Smyth, L. C. D., Highet, B., Jansson, D., Wu, J., Rustenhoven, J., Aalderink, M., Tan, A. Y. S., Li, S., Johnson, R. H., Coppieters, N., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03180-8 · Cited by 123
Basic physiology of the blood-brain barrier in health and disease: a brief overview
Kaya, M., & Ahıshalı, B. (2020) · Tissue Barriers · doi:10.1080/21688370.2020.1840913 · Cited by 126
Single-nucleus transcriptomic landscape of primate hippocampal aging
Zhang, H., Li, J., Ren, J., Sun, S., Ma, S., Zhang, W., Yu, Y., Cai, Y., Yan, K., Li, W., et al. (2021) · Protein & Cell · doi:10.1007/s13238-021-00852-9 · Cited by 122
The role of peripheral inflammatory insults in Alzheimer’s disease: a review and research roadmap
Walker, K. A., Page, L. M. L., Terrando, N., Duggan, M. R., Heneka, M. T., & Bettcher, B. M. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00627-2 · Cited by 121
Huang, D., Wang, Q., Cao, Y., Yang, H., Li, M., Wu, F., Zhang, Y., Chen, G., & Wang, Q. (2023) · ACS Nano · doi:10.1021/acsnano.2c12840 · Cited by 110
Interplay between Brain Pericytes and Endothelial Cells in Dementia
Procter, T. V., Williams, A., & Montagne, A. (2021) · The American Journal of Pathology · doi:10.1016/j.ajpath.2021.07.003 · Cited by 106
Transcytosis-enabled active extravasation of tumor nanomedicine
Zhou, Q., Li, J., Xiang, J., Shao, S., Zhou, Z., Tang, J., & Shen, Y. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114480 · Cited by 105
Strategies for Delivering Nanoparticles across Tumor Blood Vessels
Sheth, V. M., Wang, L., Bhattacharya, R., Mukherjee, P., & Wilhelm, S. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202007363 · Cited by 106
The blood–brain barrier: a help and a hindrance
Rust, R., Yin, H. R., Buil, B. A., Sagare, A. P., & Kisler, K. (2025) · Brain · doi:10.1093/brain/awaf068 · Cited by 109
Retinal Vasculopathy in Alzheimer’s Disease
Shi, H., Koronyo, Y., Rentsendorj, A., Fuchs, D.-T. S., Sheyn, J., Black, K. L., Mirzaei, N., & Koronyo‐Hamaoui, M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.731614 · Cited by 91
Busatto, S., Morad, G., Guo, P., & Moses, M. A. (2021) · FASEB BioAdvances · doi:10.1096/fba.2021-00045 · Cited by 93
The pathobiology of neurovascular aging
Santisteban, M. M., & Iadecola, C. (2025) · Neuron · doi:10.1016/j.neuron.2024.12.014 · Cited by 102
Candelario‐Jalil, E., & Paul, S. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113494 · Cited by 93
Aging biomarkers and the brain
Higgins‐Chen, A., Thrush, K., & Levine, M. E. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.01.003 · Cited by 85
Plasma dilution improves cognition and attenuates neuroinflammation in old mice
Mehdipour, M., Mehdipour, T., Skinner, C. M., Wong, N., Liu, C., Chen, C.-C., Jeon, O. H., Zuo, Y., Conboy, M. J., & Conboy, I. M. (2021) · GeroScience · doi:10.1007/s11357-020-00297-8 · Cited by 77
Preininger, M. K., & Kaufer, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116217 · Cited by 87
In vivo methods for imaging blood–brain barrier function and dysfunction
Harris, W. J., Asselin, M., Hinz, R., Parkes, L. M., Allan, S. M., Schießl, I., Boutin, H., & Dickie, B. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-022-05997-1 · Cited by 91
Li, Q., Niu, X., Yi, Y., Chen, Y., Ji, Y., Zhang, J., Li, H., Xia, Y., Wang, Y., & Deng, Z. (2022) · ACS Nano · doi:10.1021/acsnano.2c10824 · Cited by 85
Endothelial BACE1 Impairs Cerebral Small Vessels via Tight Junctions and eNOS
Zhou, H., Gao, F., Yang, X., Lin, T., Li, Z., Wang, Q., Yao, Y., Li, L., Ding, X., Shi, K., et al. (2022) · Circulation Research · doi:10.1161/circresaha.121.320183 · Cited by 82
Self-citationMicroglia protect against age-associated brain pathologies
Munro, D. A. D., Bestard-Cuche, N., McQuaid, C., Chagnot, A., Shabestari, S. K., Chadarevian, J. P., Maheshwari, U., Szymkowiak, S., Morris, K., Mohammad, M., et al. (2024) · Neuron · doi:10.1016/j.neuron.2024.05.018 · Cited by 84
Jurcău, M. C., Jurcău, A., Cristian, A., Hogea, V. O., Diaconu, R. G., & Nunkoo, V. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910535 · Cited by 100
Can exercise training teach us how to treat Alzheimer's disease?
Huuha, A. M., Norevik, C. S., Moreira, J. B. N., Kobro-Flatmoen, A., Scrimgeour, N., Kivipelto, M., Van Praag, H., Ziaei, M., Sando, S. B., Wisløff, U., et al. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101559 · Cited by 79
Brain endothelial PTEN/AKT/NEDD4-2/MFSD2A axis regulates blood-brain barrier permeability
Cui, Y., Wang, Y., Song, X., Ning, H., Zhang, Y., Teng, Y., Wang, J., & Yang, X. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109327 · Cited by 78
Ting, K. K., Coleman, P. R., Kim, H. J., Zhao, Y., Mulangala, J., Cheng, N. C., Li, W., Gunatilake, D., Johnstone, D. M., Loo, L., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00927-x · Cited by 81
Vulnerability of the Hippocampus to Insults: Links to Blood–Brain Barrier Dysfunction
Davidson, T. L., & Stevenson, R. J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25041991 · Cited by 80
The Blood–Brain Barrier: Composition, Properties, and Roles in Brain HealthPreprint
Lacoste, B., Prat, A., Andrade, M. F., & Gu, C. (2024) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041422 · Cited by 83
Mechanisms of receptor-mediated transcytosis at the blood-brain barrier
Baghirov, H. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113595 · Cited by 82
The meningeal transcriptional response to traumatic brain injury and aging
Bolte, A. C., Shapiro, D. A., Dutta, A. B., Feng, W., Bruch, K. R., Kovacs, M. A., Marco, A. R., Ennerfelt, H. E., & Lukens, J. R. (2022) · eLife · doi:10.7554/elife.81154 · Cited by 78
Shi, H., Koronyo, Y., Fuchs, D.-T. S., Sheyn, J., Wawrowsky, K., Lahiri, S., Black, K. L., & Koronyo‐Hamaoui, M. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01076-4 · Cited by 71
Kim, E. S., Jeon, M., Kim, K., Lee, S., Kim, S., & Kim, D.-G. (2021) · Viruses · doi:10.3390/v13102021 · Cited by 71
Deciphering albumin-directed drug delivery by imaging
Hu, H., Quintana, J. M., Weissleder, R., Parangi, S., & Miller, M. A. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114237 · Cited by 71
Engineering antibody and protein therapeutics to cross the blood–brain barrier
Zhao, P., Zhang, N., & An, Z. (2022) · Antibody Therapeutics · doi:10.1093/abt/tbac028 · Cited by 75
Metabolic reprogramming in ischemic stroke: when glycolytic overdrive meets lipid storm
Wang, Y., Ge, M., Wang, J., Xu, Y., Wang, N., & Xu, S. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-08114-w · Cited by 83
Annexin A1 restores cerebrovascular integrity concomitant with reduced amyloid-β and tau pathology
Ries, M., Watts, H. R., Mota, B. C., Lopez, M. Y., Donat, C. K., Baxan, N., Pickering, J. A., Chau, T. W., Semmler, A., Gurung, B., et al. (2021) · Brain · doi:10.1093/brain/awab050 · Cited by 66
Zhang, X., Wang, R., Chen, H., Jin, C., Jin, Z., Lü, J., Xu, L., Lu, Y., Zhang, J., & Shi, L. (2022) · Immunity & Ageing · doi:10.1186/s12979-022-00289-6 · Cited by 67
Glial functions in the blood-brain communication at the circumventricular organs
Miyata, S. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.991779 · Cited by 66
Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior
Barron, J. J., Mroz, N. M., Taloma, S. E., Dahlgren, M. W., Ortiz-Carpena, J. F., Keefe, M. G., Escoubas, C. C., Dorman, L. C., Vainchtein, I. D., Chiaranunt, P., et al. (2024) · Science · doi:10.1126/science.adi1025 · Cited by 71
Waste clearance shapes aging brain health
Jiang-Xie, L.-F., Drieu, A., & Kipnis, J. (2024) · Neuron · doi:10.1016/j.neuron.2024.09.017 · Cited by 66
Jiao, Y., Yang, L., Wang, R., Song, G., Fu, J., Wang, J., Gao, N., & Wang, H. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16121611 · Cited by 63
Wardlaw, J. M., Benveniste, H., & Williams, A. (2021) · Annual Review of Physiology · doi:10.1146/annurev-physiol-060821-014521 · Cited by 67
A real-time in vivo clearance assay for quantification of glymphatic efflux
Plá, V., Bork, P., Harnpramukkul, A., Olveda, G., Ladrón-de-Guevara, A., Giannetto, M. J., Hussain, R., Wang, W., Kelley, D. H., Hablitz, L. M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111320 · Cited by 64
Cui, W., Yang, X. Y., Chen, X., Xiao, D., Zhu, J., Zhang, M., Qin, X., Ma, X., & Lin, Y. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202105152 · Cited by 62
The Endothelium: An Active Regulator of Lipid and Glucose Homeostasis
Hasan, S. S., & Fischer, A. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.10.003 · Cited by 62
Investigating receptor-mediated antibody transcytosis using blood–brain barrier organoid arrays
Simonneau, C., Duschmalé, M., Gavrilov, A., Brandenberg, N., Hoehnel, S., Ceroni, C., Lassalle, E., Kassianidou, E., Knoetgen, H., Niewoehner, J., et al. (2021) · Fluids and Barriers of the CNS · doi:10.1186/s12987-021-00276-x · Cited by 65
The Blood–Brain Barrier—A Key Player in Multiple Sclerosis Disease Mechanisms
Schreiner, T. G., Romanescu, C., & Popescu, B. O. (2022) · Biomolecules · doi:10.3390/biom12040538 · Cited by 65
Wang, Y., Du, W., Hu, X., Yu, X., Guo, C., Jin, X., & Wang, W. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.08.009 · Cited by 58
Endothelial Cell Senescence Effect on the Blood-Brain Barrier in Stroke and Cognitive Impairment
Real, M. G. C., Falcione, S. R., Boghozian, R., Clarke, M., Todoran, R., Pierre, A. S., Zhang, Y., Joy, T., & Jickling, G. C. (2024) · Neurology · doi:10.1212/wnl.0000000000210063 · Cited by 60
Labarta-Bajo, L., & Allen, N. J. (2025) · Neuron · doi:10.1016/j.neuron.2024.12.010 · Cited by 62
Pan, Y., & Nicolazzo, J. A. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15802 · Cited by 49
Yang, T., Velagapudi, R., Kong, C., Ko, U., Kumar, V., Brown, P., Franklin, N. O., Zhang, X., Caceres, A. I., Min, H., et al. (2022) · British Journal of Anaesthesia · doi:10.1016/j.bja.2022.05.025 · Cited by 55
Association of microplastics in human cerebrospinal fluid with Alzheimer’s disease-related changes
He, P., Wang, F., Xi, G., Li, Y., Wang, F., Wang, H., Li, L., Ma, X., Han, Y., & Shi, Y. (2025) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2025.138748 · Cited by 60
Self-citationDesigning peptide nanoparticles for efficient brain delivery
Duro‐Castaño, A., Leite, D. M., Forth, J., Deng, Y., Matias, D., Noble-Jesus, C., & Battaglia, G. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.10.001 · Cited by 53
Location Matters: Navigating Regional Heterogeneity of the Neurovascular Unit
Bernier, L., Brunner, C., Cottarelli, A., & Balbi, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.696540 · Cited by 52
Bone-derived PDGF-BB drives brain vascular calcification in male mice
Wang, J., Fang, C., Noller, K., Wei, Z., Liu, G., Shen, K., Song, K., Cao, X., & Wan, M. (2023) · Journal of Clinical Investigation · doi:10.1172/jci168447 · Cited by 49
Pericytes Across the Lifetime in the Central Nervous System
Bennett, H. C., & Kim, Y. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.627291 · Cited by 49
Review of Design Considerations for Brain-on-a-Chip Models
Cameron, T., Bennet, T. J., Rowe, E. M., Anwer, M., Wellington, C. L., & Cheung, K. C. (2021) · Micromachines · doi:10.3390/mi12040441 · Cited by 49
A human brain vascular atlas reveals diverse cell mediators of Alzheimer’s disease risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Maat, C. A., Losada, P. M., Chen, M. B., Agam, M., Schaum, N., Khoury, N., et al. (2021) · doi:10.1101/2021.04.26.441262 · Cited by 48
Self-citationLi, Y., Wu, H., Jiang, X., Dong, Y.-F., Zheng, J., & Gao, J. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.04.001 · Cited by 47
Brain Delivery of Nanomedicines: Trojan Horse Liposomes for Plasmid DNA Gene Therapy of the Brain
Pardridge, W. M. (2020) · Frontiers in Medical Technology · doi:10.3389/fmedt.2020.602236 · Cited by 46
Han, G., Bai, K., Yang, X., Sun, C., Ji, Y., Zhou, J., Zhang, H., & Ding, Y. (2022) · Advanced Science · doi:10.1002/advs.202106072 · Cited by 46
The Growing Class of Novel RNAi Therapeutics
Traber, G. M., & Yu, A. (2024) · Molecular Pharmacology · doi:10.1124/molpharm.124.000895 · Cited by 51
Self-citationMoyer, T. C., Hoffman, B. A., Chen, W., Shah, I. S., Ren, X., Knox, T. M., Liu, J., Wang, W., Li, J., Khalid, H., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.04.046 · Cited by 64
Self-citationCaveolae-Mediated Endothelial Transcytosis across the Blood-Brain Barrier in Acute Ischemic Stroke
Zhou, M., Shi, S. X.-Y., Liu, N., Jiang, Y., Karim, M. S., Vodovoz, S. J., Wang, X., Zhang, B., & Dumont, A. S. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10173795 · Cited by 48
Structural and molecular basis of choline uptake into the brain by FLVCR2
Cater, R. J., Mukherjee, D., Gil-Iturbe, E., Erramilli, S. K., Chen, T., Koo, K., Santander, N., Reckers, A., Kloss, B., Gawda, T., et al. (2024) · Nature · doi:10.1038/s41586-024-07326-y · Cited by 45
Current Update on Transcellular Brain Drug Delivery
Pawar, B., Vasdev, N., Gupta, T., Mhatre, M., More, A., Anup, N., & Tekade, R. K. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14122719 · Cited by 50
Metadata
- Authors
- Yang, A. C., Stevens, M. Y., Chen, M. B., Lee, D. P., Stähli, D., Gate, D., Contrepois, K., Chen, W., Iram, T., Zhang, L., Vest, R. T., Chaney, A., Lehallier, B., Olsson, N., du Bois, H., Hsieh, R., Cropper, H. C., Berdnik, D., Li, L., Wang, E. Y., Traber, G. M., Bertozzi, C. R., Luo, J., Snyder, M. P., Elias, J. E., Quake, S. R., James, M. L., & Wyss-Coray, T.
- Affiliations
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- VA Palo Alto Health Care System (US)
- ORCID
- Yang, Andrew C.
- Stevens, Marc Y.
- Gate, David
- Contrepois, Kévin
- Chen, Winnie
- Iram, Tal
- Zhang, Lichao
- Chaney, Aisling
- Lehallier, Benoit
- Olsson, Niclas
- Cropper, Haley C.
- Berdnik, Daniela
- Li, Lulin
- Wang, Elizabeth Y.
- Traber, Gavin M.
- Bertozzi, Carolyn R.
- Luo, Jian
- Snyder, Michael P.
- Elias, Joshua E.
- Quake, Stephen R.
- James, Michelle L.
- Wyss-Coray, Tony
- Venue
- Nature
- Published
- 2020-07-01
- Volume
- 583
- Issue
- 7816
- Pages
- 425-430
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC8331074
- OpenAlex
- W3039975419
- Cited by
- 477
- References
- 96
- Citations by year
- 2026: 63 · 2025: 91 · 2024: 83 · 2023: 69 · 2022: 75 · 2021: 74 · 2020: 22
- FWCI
- 23.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association (19PABHI34580007)
- Glenn Foundation for Medical Research
- NOMIS Stiftung
- National Institutes of Health (1s10od025091-01, T32-AG0047126)
- Wu Tsai Neurosciences Institute, Stanford University
- National Institute on Aging (RF1AG059694, DP1AG053015, T32AG047126, P30AG066515)
- National Human Genome Research Institute (P50HG007735)
- National Cancer Institute (R01CA200423)
- National Institute of General Medical Sciences (T32GM099608, GM059907, R01GM059907)
- National Center for Research Resources (1S10OD01227601)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- blood-brain barrier, brain aging, transcytosis, receptor-mediated transport, pericyte coverage, ALPL, transferrin, transferrin receptor, plasma proteome, brain endothelium, BBB dysfunction, brain drug delivery
- MeSH terms
- Aging, Alkaline Phosphatase, Animals, Antibodies, Biological Transport, Blood Proteins, Blood-Brain Barrier, Brain, Health, Humans, Male, Mice, Inbred C57BL, Plasma, Receptors, Transferrin, Transcription, Genetic, Transferrin, Drug Delivery Systems, Proteome, Mice, Transcytosis
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
