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
Items 101–200 of 482
Liu, G., Wang, J., Wei, Z., Fang, C., Shen, K., Cheng, Q., Qi, C., Li, T., Gao, P., Wong, P. C., et al. (2023) · Advanced Science · doi:10.1002/advs.202206938 · Cited by 44
The blood-brain barrier, a key bridge to treat neurodegenerative diseases
Hang, Z., Zhou, L., Xing, C., Wen, Y., & Du, H. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102070 · Cited by 46
Disruption of the cerebrospinal fluid–plasma protein balance in cognitive impairment and aging
Farinas, A., Rutledge, J., Bot, V. A., Western, D., Ying, K., Lawrence, K. A., Oh, H. S., Yoon, S., Ding, D. Y., Tsai, A. P., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03831-3 · Cited by 52
Self-citationNext-generation in vitro blood–brain barrier models: benchmarking and improving model accuracy
Linville, R. M., & Searson, P. C. (2021) · Fluids and Barriers of the CNS · doi:10.1186/s12987-021-00291-y · Cited by 43
Public Volume Electron Microscopy Data: An Essential Resource to Study the Brain Microvasculature
Bonney, S. K., Coelho‐Santos, V., Huang, S., Takeno, M. M., Kornfeld, J. M. R., Keller, A., & Shih, A. Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.849469 · Cited by 43
Cellular senescence and the blood–brain barrier: Implications for aging and age-related diseases
Knopp, R. C., Erickson, M. A., Rhea, E. M., Reed, M. J., & Banks, W. A. (2023) · Experimental Biology and Medicine · doi:10.1177/15353702231157917 · Cited by 47
Molledo, M. M., Nji, E., & Reyes, N. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00786-8 · Cited by 41
Zhang, J., Sun, X. Y., Li, H., Ma, H., Duan, F., Wu, Z., Zhu, B., Chen, R., & Nie, L. (2023) · Photoacoustics · doi:10.1016/j.pacs.2023.100462 · Cited by 41
Brain iron acquisition: An overview of homeostatic regulation and disease dysregulation
Baringer, S. L., Simpson, I. A., & Connor, J. R. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15819 · Cited by 41
Receptor–mediated transcytosis of macromolecules across the blood–brain barrier
Baghirov, H. (2023) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2023.2255138 · Cited by 44
Unveiling the impact of aging on BBB and Alzheimer's disease: Factors and therapeutic implications
Jha, N. K., Jha, N. K., Nuli, M. V., Gupta, S. K., Kanna, S., Gahtani, R. M., Hani, U., Singh, A. K., Abomughaid, M. M., Abomughayedh, A. M., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102224 · Cited by 43
Shamul, J. G., Wang, Z., Gong, H., Ou, W., White, A. M., Garcia, D. P. M., Gu, S., Clyne, A. M., Quiñones‐Hinojosa, A., & He, X. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01250-2 · Cited by 43
Xie, K., Fuchs, H., Scifo, E., Liu, D., Aziz, N. A., Aguilar‐Pimentel, J. A., Amarie, O. V., Becker, L., da Silva‐Buttkus, P., Calzada‐Wack, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34515-y · Cited by 42
Historical and current perspectives on blood endothelial cell heterogeneity in the brain
Matsuoka, R. L., Buck, L. D., Vajrala, K. P., Quick, R. E., & Card, O. A. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04403-1 · Cited by 40
Singh, P. P., Reeves, G. A., Contrepois, K., Papsdorf, K., Miklas, J. W., Ellenberger, M., Hu, C., Snyder, M. P., & Brunet, A. (2024) · Cell · doi:10.1016/j.cell.2024.04.048 · Cited by 41
Self-citationDynamic modulation of the blood–brain barrier in the healthy brain
Friedman, A., Prager, O., Serlin, Y., & Kaufer, D. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00976-5 · Cited by 48
Anoctamin-2-specific T cells link Epstein-Barr virus to multiple sclerosis
Thomas, O. G., Rykaczewska, U., Galesic, M., van der Burgt, R. T. M., Hallen, N., Ferro, F., Bronge, M., Marti, Z., Li, Y., Rique, A. H., et al. (2026) · Cell · doi:10.1016/j.cell.2025.12.032 · Cited by 41
Barkaway, A., Attwell, D., & Korte, N. (2022) · Neurophotonics · doi:10.1117/1.nph.9.3.031914 · Cited by 38
Blood-brain barrier pathology in cerebral small vessel disease
Jia, R., Guardia, G. S., & Kiliaan, A. J. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385864 · Cited by 42
Blood-Brain Barrier Disruption: A Common Driver of Central Nervous System Diseases
Segura‐Collar, B., Mata-Martínez, P., Hernández‐Laín, A., Sánchez‐Gómez, P., & Gargini, R. (2021) · The Neuroscientist · doi:10.1177/1073858420985838 · Cited by 39
Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas
Wei, X., Meel, M. H., Breur, M., Bugiani, M., Hulleman, E., & Phoenix, T. N. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01243-1 · Cited by 39
Urayama, A., Moreno-Gonzalez, I., Morales-Scheihing, D., Kharat, V., Pritzkow, S., & Soto, C. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01679-4 · Cited by 37
Sun, B., Li, L., Harris, O. A., & Luo, J. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00478-5 · Cited by 44
Self-citationLee, S. H., Park, S., Yeo, S. S., Kwon, O., Lee, M., Yoo, H.-R., Ahn, E. K., Jang, J. Y., & Jang, J.-H. (2022) · Diagnostics · doi:10.3390/diagnostics12010112 · Cited by 37
Transcellular routes of blood–brain barrier disruption
Erickson, M. A., & Banks, W. A. (2022) · Experimental Biology and Medicine · doi:10.1177/15353702221080745 · Cited by 37
Can the administration of platelet lysates to the brain help treat neurological disorders?
Nebie, O., Buée, L., Blum, D. L., & Burnouf, T. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04397-w · Cited by 37
Lee, J., Lee, H., Lee, H. G., Shin, M., Shin, M.-G., Seo, J., Lee, E. J., Park, S. A., & Park, S. (2023) · Nature Communications · doi:10.1038/s41467-023-44319-3 · Cited by 37
Cerebrovascular Anomalies: Perspectives From Immunology and Cerebrospinal Fluid Flow
Rustenhoven, J., Tanumihardja, C., & Kipnis, J. (2021) · Circulation Research · doi:10.1161/circresaha.121.318173 · Cited by 38
Alam, P., Holst, M. R., Lauritsen, L., Nielsen, J., Nielsen, S. S. E., Jensen, P. H., Brewer, J. R., Otzen, D. E., & Nielsen, M. S. (2022) · Fluids and Barriers of the CNS · doi:10.1186/s12987-022-00334-y · Cited by 32
Bellaver, B., Puig‐Pijoan, A., Ferrari‐Souza, J. P., Leffa, D. T., Lussier, F. Z., Ferreira, P. C. L., Tissot, C., Povala, G., Therriault, J., Benedet, A. L., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13014 · Cited by 36
You, T.-Y., Dong, Q., & Cui, M. (2022) · Aging and Disease · doi:10.14336/ad.2022.1204 · Cited by 33
Kato, R., Zeng, W., Siramshetty, V. B., Williams, J. W., Kabir, M., Hagen, N. R., Padilha, E. C., Wang, A. Q., Mathé, E. A., Xu, X., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1291246 · Cited by 37
Nanotechnology to Overcome Blood–Brain Barrier Permeability and Damage in Neurodegenerative Diseases
Jiménez, A., Estudillo, E., Guzmán‐Ruiz, M. A., Herrera, N., Victoria-Acosta, G., Cortés-Malagón, E. M., & López-Ornelas, A. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17030281 · Cited by 36
The Blood-Brain Barrier in Alzheimer’s Disease
Storck, S. E., Hartz, A. M. S., & Pietrzik, C. U. (2020) · Handbook of experimental pharmacology · doi:10.1007/164_2020_418 · Cited by 31
Mamtilahun, M., Jiang, L., Song, Y., Shi, X., Liu, C., Jiang, Y., Deng, L., Zheng, H., Shen, H., Li, Y., et al. (2021) · Stroke and Vascular Neurology · doi:10.1136/svn-2020-000774 · Cited by 33
Zhukov, O., He, C., Soylu-Kucharz, R., Cai, C., Lauritzen, A. D., Aldana, B. I., Björkqvist, M., Lauritzen, M., & Kucharz, K. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1089005 · Cited by 30
Brain aging and rejuvenation at single-cell resolution
Sun, E., Nagvekar, R., Pogson, A. N., & Brunet, A. (2025) · Neuron · doi:10.1016/j.neuron.2024.12.007 · Cited by 35
Endothelial TDP-43 depletion disrupts core blood–brain barrier pathways in neurodegeneration
Omar, O. M., Kimble, A. L., Ashok, C., Tyburski, J. D., Pandey, S., Wu, Q., Reese, B., Jellison, E. R., Hao, B., Li, Y., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01914-5 · Cited by 40
Protein glycosylation in urine as a biomarker of diseases
Xu, M., Yang, A., Xia, J., Jiang, J., Liu, C., Ye, Z., Ma, J., & Yang, S. (2022) · Translational research · doi:10.1016/j.trsl.2022.08.001 · Cited by 31
Self-citationWang, P., Konja, D., Singh, S., Zhang, B., & Wang, Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25041978 · Cited by 37
Blood brain barrier dysfunction in healthy aging and dementia: Why, how, what for?
Cunha, S., Bicker, J., Sereno, J., Falcão, A. C., & Fortuna, A. C. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102395 · Cited by 31
Advanced translational PBPK model for transferrin receptor-mediated drug delivery to the brain
Sato, S., Liu, S., Goto, A., Yoneyama, T., Okita, K., Yamamoto, S., Hirabayashi, H., Iwasaki, S., & Kusuhara, H. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.04.012 · Cited by 33
Circadian Mechanisms in Brain Fluid Biology
Vizcarra, V. S., Fame, R. M., & Hablitz, L. M. (2024) · Circulation Research · doi:10.1161/circresaha.123.323516 · Cited by 31
Blood–brain barrier dysfunction in aging is mediated by brain endothelial senescence
Novo, J. P., Gee, L. E., Caetano, C., Tomé, I., Vilaça, A., von Zglinicki, T., Moreira, I. S., Jurk, D., Rosa, S. C., & Ferreira, L. (2024) · Aging Cell · doi:10.1111/acel.14270 · Cited by 32
Liver exerkine reverses aging- and Alzheimer’s-related memory loss via vasculature
Bieri, G., Pratt, K. J. B., Fuseya, Y., Aghayev, T., Sucharov, J., Horowitz, A. M., Philp, A. R., Fonseca-Valencia, K., Chu, R., Phan, M., et al. (2026) · Cell · doi:10.1016/j.cell.2026.01.024 · Cited by 35
Self-citationCortical cerebrovascular and metabolic perturbations in the 5xFAD mouse model of Alzheimer’s disease
Jullienne, A., Szu, J. I., Quan, R., Trinh, M. V., Norouzi, T., Noarbe, B. P., Bedwell, A. A., Eldridge, K., Persohn, S. A., Territo, P. R., et al. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1220036 · Cited by 30
Fan, Y., Yuan, J., Somekh, J., Mor Peleg, B., Zhu, Y., Jia, Z., Wu, F. L., & Huang, Z. (2025) · Science Advances · doi:10.1126/sciadv.adr3757 · Cited by 30
Blood–brain borders: a proposal to address limitations of historical blood–brain barrier terminology
Badaut, J., Ghersi‐Egea, J., Thorne, R. G., & Konsman, J. P. (2024) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00478-5 · Cited by 31
The influence of physiological and pathological perturbations on blood-brain barrier function
Zhao, N., Chung, T. D., Guo, Z., Jamieson, J. J., Liang, L. R., Linville, R. M., Pessell, A. F., Wang, L., & Searson, P. C. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1289894 · Cited by 31
Macrophage-derived CTSS drives the age-dependent disruption of the blood-CSF barrier
Chen, Y., Zhou, Y., Bai, Y., Jia, K., Zhang, H., Chen, Q., Song, M., Dai, Y., Shi, J., Chen, Z., et al. (2025) · Neuron · doi:10.1016/j.neuron.2025.01.023 · Cited by 29
Baker, T. L., Agoston, D. V., Brady, R. D., Major, B. P., McDonald, S. J., Mychasiuk, R., Wright, D. K., Yamakawa, G. R., Sun, M., & Shultz, S. R. (2021) · The Neuroscientist · doi:10.1177/10738584211012264 · Cited by 28
Integrative analysis of the human brain mural cell transcriptome
Gastfriend, B. D., Foreman, K. L., Katt, M. E., Palecek, S. P., & Shusta, E. V. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x211013700 · Cited by 28
Yang, J. M., Yun, K., Jeon, J., Yang, H. Y., Kim, B., Jeong, S., Lee, J., Oh, W., Uemura, A., Song, J. S., et al. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00733-z · Cited by 28
Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction
Hansen, C. E., Vacondio, D., van der Molen, L., Jüttner, A. A., Fung, W. K., Karsten, M., van het Hof, B., Fontijn, R. D., Kooij, G., Witte, M. E., et al. (2025) · Cell Death & Disease · doi:10.1038/s41419-024-07306-0 · Cited by 27
Characterization of the blood–brain barrier in genetically diverse laboratory mouse strains
Schaffenrath, J., Huang, S., Wyss, T., Delorenzi, M., & Keller, A. (2021) · Fluids and Barriers of the CNS · doi:10.1186/s12987-021-00269-w · Cited by 29
Wang, J., Xu, J., Zang, G., Zhang, T., Wu, Q., Zhang, H., Chen, Y., Wang, Y., Qin, W., Zhao, S., et al. (2022) · Research · doi:10.34133/2022/9839368 · Cited by 27
PCSK9 inhibition attenuates alcohol-associated neuronal oxidative stress and cellular injury
Wagner, J., Park, L. M., Mukhopadhyay, P., Matyas, C., Trojnar, E., Damadzic, R., Jung, J., Bell, A. S., Mavromatis, L. A., Hamandi, A. M., et al. (2024) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2024.04.022 · Cited by 26
Xu, M., Cao, R., Hao, B., Wang, D., Luo, D., Dou, H., & Chen, Z. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202407380 · Cited by 26
Advanced Noninvasive Strategies for the Brain Delivery of Therapeutic Proteins and Peptides
Lin, J., Yu, Z., & Gao, X. (2024) · ACS Nano · doi:10.1021/acsnano.4c06851 · Cited by 28
Muscat, S. M., & Barrientos, R. M. (2021) · Brain Plasticity · doi:10.3233/bpl-210127 · Cited by 26
Influence of traumatic brain injury on extracellular tau elimination at the blood–brain barrier
Eisenbaum, M., Pearson, A., Gratkowski, A., Mouzon, B., MULLAN, M. J., Crawford, F., Ojo, J. O., & Bachmeier, C. J. (2021) · Fluids and Barriers of the CNS · doi:10.1186/s12987-021-00283-y · Cited by 26
Cummings, J. L., Schwartz, G. G., Nicholls, S. J., Khan, A., Halliday, C., Toth, P. P., Sweeney, M., Johansson, J. O., Wong, N. C. W., Kulikowski, E., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210570 · Cited by 25
Age, dose, and binding to TfR on blood cells influence brain delivery of a TfR-transported antibody
Faresjö, R., Sehlin, D., & Syvänen, S. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00435-2 · Cited by 23
Völgyi, K., González-Gallego, J., Müller, S. A., Beaufort, N., Malik, R., Schifferer, M., Todorov, M. I., Crusius, D., Robinson, S., Schmidt, A., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00598-z · Cited by 25
Trevino, T. N., Almousawi, A. A., Robinson, K. F., Fogel, A., Class, J., Minshall, R. D., Tai, L. M., Richner, J. M., & Lutz, S. E. (2024) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2024.578309 · Cited by 25
Aryal, R., & Patabendige, A. (2021) · Open Biology · doi:10.1098/rsob.200396 · Cited by 24
The Interplay Between Brain Vascular Calcification and Microglia
Maheshwari, U., Huang, S., Sridhar, S., & Keller, A. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.848495 · Cited by 24
Central nervous system vascularization in human embryos and neural organoids
Boutom, S., Silva, T. P., Palecek, S. P., Shusta, E. V., Fernandes, T. G., & Ashton, R. S. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.115068 · Cited by 26
Advanced nanoparticle engineering for precision therapeutics of brain diseases
Ismail, M., Liu, J., Wang, N., Zhang, D., Qin, C., Shi, B., & Zheng, M. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123138 · Cited by 28
Microvascular basis of cognitive impairment in type 1 diabetes
Sharma, S., & Brown, C. E. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107929 · Cited by 24
Blood-brain barrier biomarkers
Zapata-Acevedo, J. F., Mantilla-Galindo, A., Vargas-Sánchez, K., & González-Reyes, R. E. (2024) · Advances in clinical chemistry · doi:10.1016/bs.acc.2024.04.004 · Cited by 23
Choi, E. S., & Shusta, E. V. (2023) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2023.2286371 · Cited by 25
Blood–Brain Barrier: Structure, Function, Diseases, and Drug Delivery Systems
He, Y., Qu, M., Yu, L., He, L., Lu, Y., Hong, J., Sun, M., Yang, H., Mi, W., Guo, H., et al. (2026) · MedComm · doi:10.1002/mco2.70712 · Cited by 24
Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets
Zheng, P., Yan, W., Ding, Y.-N., Zhang, Y., Chen, Z., Qian, J., & Ge, J. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02630-7 · Cited by 26
Nociceptor-derived Reg3γ prevents endotoxic death by targeting kynurenine pathway in microglia
Sugisawa, E., Kondo, T., Kumagai, Y., Kato, H., Takayama, Y., Isohashi, K., Shimosegawa, E., Takemura, N., Hayashi, Y., Sasaki, T., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110462 · Cited by 23
The vasculature of neurogenic niches: Properties and function
Karakatsani, A., Álvarez-Vergara, M. I., & de Almodóvar, C. R. (2023) · Cells and Development · doi:10.1016/j.cdev.2023.203841 · Cited by 25
Bats, M., Peghaire, C. R., Delobel, V., Dufourcq, P., Couffinhal, T., & Duplàa, C. (2022) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041219 · Cited by 24
The Role of BAR Proteins and the Glycocalyx in Brain Endothelium Transcytosis
Leite, D. M., Matias, D., & Battaglia, G. (2020) · Cells · doi:10.3390/cells9122685 · Cited by 23
Pathways linking Alzheimer’s disease risk genes expressed highly in microglia
Hodges, A. K., Piers, T. M., Collier, D., Cousins, O., & Pocock, J. M. (2021) · Neuroimmunology and Neuroinflammation · doi:10.20517/2347-8659.2020.60 · Cited by 21
Anesthesia triggers drug delivery to experimental glioma in mice by hijacking caveolar transport
Spieth, L., Berghoff, S. A., Stumpf, S. K., Winchenbach, J., Michaelis, T., Watanabe, T., Gerndt, N., Düking, T., Hofer, S., Ruhwedel, T., et al. (2021) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdab140 · Cited by 22
Watson, L. S., Wilken-Resman, B., Williams, A., DiLucia, S., Sánchez, G., McLeod, T., & Sims‐Robinson, C. (2022) · Diabetes and Vascular Disease Research · doi:10.1177/14791641221118626 · Cited by 26
López-Ornelas, A., Jiménez, A., Pérez‐Sánchez, G., Rodríguez-Pérez, C. E., Corzo‐Cruz, A., Velasco, I., & Estudillo, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231710136 · Cited by 22
Advances in the research of nano delivery systems in ischemic stroke
Li, Y., Wang, H., Jin, J., Yang, C., Hu, J., & Li, J. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.984424 · Cited by 21
Bystanders or not? Microglia and lymphocytes in aging and stroke
Chauhan, A., & Nguyen, J. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.360345 · Cited by 21
Vascular endothelial cells: a fundamental approach for brain waste clearance
Wei, H., Jiang, H., Zhou, Y., Xiao, X., Zhou, C., & Ji, X. (2022) · Brain · doi:10.1093/brain/awac495 · Cited by 20
Wang, Y., Du, W., Sun, Y., Zhang, J., Ma, C., & Jin, X. (2023) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x231169133 · Cited by 24
Cooperation between neurovascular dysfunction and Aβ in Alzheimer’s disease
Wang, N., Yang, X., Zhao, Z., Liu, D., Wang, X., Tang, H., Zhong, C., Chen, X., Chen, W. K., & Meng, Q. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1227493 · Cited by 22
Self-citationImmune control of brain physiology
Kovacs, M., Dominguez-Belloso, A., Ali-Moussa, S., & Deczkowska, A. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-025-01129-6 · Cited by 22
The blood–brain barrier as a treatment target for neurodegenerative disorders
Rust, R., Sagare, A. P., Zhang, M., Zloković, B. V., & Kisler, K. (2025) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2025.2480654 · Cited by 21
Kim, S., Jung, C., Lee, J. Y., Kim, G., Choi, S. W., Jin, H. J., & Park, H. (2020) · Allergy · doi:10.1111/all.14609 · Cited by 20
Pediatric Brain Tumours: Lessons from the Immune Microenvironment
Yao, B., Delaidelli, A., Vogel, H. S., & Sorensen, P. H. B. (2023) · Current Oncology · doi:10.3390/curroncol30050379 · Cited by 21
Scalisi, J., Balau, B., Deneyer, L., Bouchat, J., Gilloteaux, J., & Nicaise, C. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.135665 · Cited by 20
Caveolae-Mediated Transcytosis and Its Role in Neurological Disorders
Yang, K., Li, Q., Ruan, Y., Xia, Y., & Fang, Z. H. (2025) · Biomolecules · doi:10.3390/biom15040456 · Cited by 20
Liu, Y., Wang, Q., Feng, Z., Qin, M., Zhang, Z., Jiang, J., Ren, T., Liu, X., Brinker, C. J., Zhao, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61434-5 · Cited by 21
Nwafor, D. C., Brichacek, A. L., Ali, A., & Brown, C. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105257 · Cited by 22
Breaking barriers in postoperative delirium
Terrando, N., & Akassoglou, K. (2022) · British Journal of Anaesthesia · doi:10.1016/j.bja.2022.05.004 · Cited by 19
Single-particle imaging of nanomedicine entering the brain
Wei, M., Qian, N., Gao, X., Lang, X., Song, D., & Min, W. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2309811121 · Cited by 19
A high-resolution view of the heterogeneous aging endothelium
Dobner, S., Tóth, F., & de Rooij, L. P. M. H. (2024) · Angiogenesis · doi:10.1007/s10456-023-09904-6 · Cited by 23
Ren, Y., Shen, Y., Si, N., Fan, S., Zhang, Y., Xu, W., Shi, L., & Zhang, X. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.639935 · Cited by 21
Cerium-based nanoparticles for neurodegeneration: emerging redox therapeutics beyond pharmaceuticals
Mishra, K., Tripathi, S., Tiwari, A. K., Rana, R., Yadav, P., & Chourasia, M. K. (2025) · RSC Advances · doi:10.1039/d5ra03599f · Cited by 20
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
