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Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance
Open accessAbstract
PICALM is a highly validated genetic risk factor for Alzheimer's disease (AD). We found that reduced expression of PICALM in AD and murine brain endothelium correlated with amyloid-β (Aβ) pathology and cognitive impairment. Moreover, Picalm deficiency diminished Aβ clearance across the murine blood-brain barrier (BBB) and accelerated Aβ pathology in a manner that was reversible by endothelial PICALM re-expression. Using human brain endothelial monolayers, we found that PICALM regulated PICALM/clathrin-dependent internalization of Aβ bound to the low density lipoprotein receptor related protein-1, a key Aβ clearance receptor, and guided Aβ trafficking to Rab5 and Rab11, leading to Aβ endothelial transcytosis and clearance. PICALM levels and Aβ clearance were reduced in AD-derived endothelial monolayers, which was reversible by adenoviral-mediated PICALM transfer. Inducible pluripotent stem cell-derived human endothelial cells carrying the rs3851179 protective allele exhibited higher PICALM levels and enhanced Aβ clearance. Thus, PICALM regulates Aβ BBB transcytosis and clearance, which has implications for Aβ brain homeostasis and clearance therapy.
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“Similarly, several genes reported to be involved in Aβ catabolism, such as RAB5A, RAB11A, CLU, and LRP2 (49–53), were also down-regulated in AD monocytes, suggesting the impaired Aβ catabolism in AD monocytes.”
From Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems (2025) · cites this paper as [51]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“PICALM is enriched in the endothelium of human cerebral vessels including capillaries, but is downregulated in AD patients (683).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [683]
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In the citing paper
“PICALM controls receptor internalization and subsequent intracellular trafficking (683), via R-SNARE-mediated fusion of clathrin-coated vesicles with endosomes (411).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [683]
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In the citing paper
“Specifically, LRP1 facilitates clathrin-dependent, receptor-mediated endothelial endocytosis of A 𝛃 at the abluminal membrane of the BBB, which requires phosphatidylinositol binding clathrin assembly protein (PICALM) (683).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [683]
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In the citing paper
“PICALM guides transendothelial trafficking of endocytotic A 𝛃 -containing vesicles to Rab5, and then to Rab11 small GTPase leading to exocytosis of A 𝛃 across the luminal membrane of the BBB into the blood (683).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [683]
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In the citing paper
“As shown in the Picalm + / -; APP Swe mice, diminished PICALM levels at the BBB accelerate amyloid pathology and behavioral deficits, which can be ameliorated by endothelial re-expression of Picalm using an adeno-associated virus (AAV) (683).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [683]
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In the citing paper
“Endothelial cells derived from human iPSCs carrying homozygous protective rs3851179 A alleles exhibited increased PICALM expression and improved transvascular clearance of A 𝛃 across human BBB in vitro, when compared with isogenic cells from iPSCs carrying homozygous risk rs3851179 G alleles (683).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [683]
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In the citing paper
“Although most of the PICALM single nucleotide variants (SNPs) associated with late-onset AD are located outside of the coding regions (683), the risk alleles of rs3851179 (236) and rs10792832 (344) lead to lower expression of PICALM isoform 2 in the frontal and temporal cortex in the human brain on the expression quantitative trait loci (eQTLs) (586), indicating that lower PICALM levels may”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [683]
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In the citing paper
“These functions are central to its role in the clearance of both tau through autophagy (423) and A 𝛃 via transvascular transport across the BBB (683).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [683]
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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 [15]
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“More recently, PICALM has been described in vitro and in vivo to participate to Aβ transcytosis and clearance at the BBB through clathrin-dependent internalisation of Aβ after its binding to the LDLR-related protein-1 [157].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [157]
In the citing paper
“For previously reported loci, applying the same prioritization approach highlights several genes, as described in Fig. 2, some of which are involved in APP metabolism (FERMT2, PICALM) or tau toxicity (BIN1, CD2AP, FERMT2, CASS4, PTK2B)98–101.”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [101]
In the citing paper
“Several genes encoding proteins intimately associated with the endothelium and Aβ clearance are highly validated AD risk factors, such as APOEε4, PICALM, and CLU [50, 51].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [51]
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Cites
1 retracted
RETRACTED ARTICLE: Pericyte loss influences Alzheimer-like neurodegeneration in mice
Sagare, A. P., Bell, R. D., Zhao, Z., Ma, Q., Winkler, E. A., Ramanathan, A., & Zlokovic, B. V. (2013) · Nature Communications · doi:10.1038/ncomms3932 · Cited by 589
Self-citationRetractedThe 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
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210
Rab GTPases as coordinators of vesicle traffic
Stenmark, H. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2728 · Cited by 3,413
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
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969
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Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076
Self-citationAlzheimer Disease Genetics Consortium (ADGC), Kunkle, B. W., The European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, P. A. E. R. F. A. D. C. (., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0358-2 · Cited by 2,946
The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
Iadecola, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.030 · Cited by 2,480
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Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,312
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Aspelund, A., Antila, S., Proulx, S. T., Karlsen, T. V., Karaman, S., Detmar, M., Wiig, H., & Alitalo, K. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20142290 · Cited by 2,198
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De Strooper, B., & Karran, E. (2016) · Cell · doi:10.1016/j.cell.2015.12.056 · Cited by 1,990
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Kadry, H., Noorani, B., & Cucullo, L. (2020) · Fluids and Barriers of the CNS · doi:10.1186/s12987-020-00230-3 · Cited by 1,853
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Zhao, Z., Nelson, A. R., Betsholtz, C., & Zlokovic, B. V. (2015) · Cell · doi:10.1016/j.cell.2015.10.067 · Cited by 1,670
Self-citationFunctional aspects of meningeal lymphatics in ageing and Alzheimer’s disease
Da Mesquita, S., Louveau, A., Vaccari, A., Smirnov, I., Cornelison, R. C., Kingsmore, K. M., Contarino, C., Onengut-Gumuscu, S., Farber, E., Raper, D., et al. (2018) · Nature · doi:10.1038/s41586-018-0368-8 · Cited by 1,445
Helms, H. C., Abbott, N. J., Burek, M., Cecchelli, R., Couraud, P.-O., Deli, M. A., Förster, C., Galla, H. J., Romero, I. A., Shusta, E. V., et al. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16630991 · Cited by 843
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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
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Keaney, J., & Campbell, M. (2015) · The FEBS Journal · doi:10.1111/febs.13412 · Cited by 616
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Nelson, A. R., Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.12.016 · Cited by 559
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Da Mesquita, S., Fu, Z., & Kipnis, J. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.022 · Cited by 479
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Storck, S. E., Meister, S., Nahrath, J., Meißner, J. N., Schubert, N., Di Spiezio, A., Baches, S., Vandenbroucke, R. E., Bouter, Y., Prikulis, I., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81108 · Cited by 477
Yin, F. (2023) · The FEBS Journal · doi:10.1111/febs.16344 · Cited by 441
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Henstridge, C. M., Hyman, B. T., & Spires-Jones, T. L. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0113-1 · Cited by 348
Montagne, A., Nikolakopoulou, A. M., Zhao, Z., Sagare, A. P., Si, G., Lazic, D., Barnes, S. R., Daianu, M., Ramanathan, A., Go, A., et al. (2018) · Nature Medicine · doi:10.1038/nm.4482 · Cited by 344
Self-citationRetractedA single-cell atlas of the normal and malformed human brain vasculature
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Giri, M., Lü, Y., & Zhang, M. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s105769 · Cited by 311
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Bowman, G. L., Dayon, L., Kirkland, R. E., Wojcik, J., Peyratout, G., Severin, I. C., Henry, H., Oikonomidi, A., Migliavacca, E., Bacher, M., et al. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.06.2857 · Cited by 307
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Ma, Q., Zhao, Z., Sagare, A. P., Wu, Y., Wang, M., Owens, N. C., Verghese, P. B., Herz, J., Holtzman, D. M., & Zlokovic, B. V. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0286-0 · Cited by 281
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Govindpani, K., McNamara, L. G., Smith, N. R., Vinnakota, C., Waldvogel, H. J., Faull, R. L. M., & Kwakowsky, A. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8050651 · Cited by 281
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Rustenhoven, J., & Kipnis, J. (2022) · Nature · doi:10.1038/s41586-022-05474-7 · Cited by 253
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Greene, C., & Campbell, M. (2016) · Tissue Barriers · doi:10.1080/21688370.2015.1138017 · Cited by 254
Zhou, W., Chen, C., Shi, Y., Wu, Q., Gimple, R. C., Fang, X., Huang, Z., Zhai, K., Ke, S. Q., Ping, Y., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.10.002 · Cited by 235
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Pimenova, A. A., Raj, T., & Goate, A. M. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.05.014 · Cited by 223
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Clearance of Amyloid Beta and Tau in Alzheimer’s Disease: from Mechanisms to Therapy
Xin, S.-H., Tan, L., Cao, X., Yu, J.-T., & Tan, L. (2018) · Neurotoxicity Research · doi:10.1007/s12640-018-9895-1 · Cited by 222
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Villaseñor, R., Lampe, J., Schwaninger, M., & Collin, L. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2982-x · Cited by 221
Li, Y., Zhang, J., Wan, J., Liu, A., & Sun, J. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110887 · Cited by 214
Hladky, S. B., & Barrand, M. A. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0113-6 · Cited by 206
Ramanathan, A., Nelson, A. R., Sagare, A. P., & Zlokovic, B. V. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00136 · Cited by 205
Self-citationHuman pluripotent stem cell–derived brain pericyte–like cells induce blood-brain barrier properties
Stebbins, M. J., Gastfriend, B. D., Canfield, S. G., Lee, M.-S., Richards, D., Faubion, M. G., Li, W.-J., Daneman, R., Palecek, S. P., & Shusta, E. V. (2019) · Science Advances · doi:10.1126/sciadv.aau7375 · Cited by 195
Gao, X., Yue, Q., Liu, Z., Ke, M., Zhou, X., Li, S., Zhang, J., Zhang, R., Chen, L., Mao, Y. Q., et al. (2017) · Advanced Materials · doi:10.1002/adma.201603917 · Cited by 194
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Verheijen, J., & Sleegers, K. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.02.007 · Cited by 192
Montagne, A., Nikolakopoulou, A. M., Huuskonen, M. T., Sagare, A. P., Lawson, E. J., Lazic, D., Rege, S. V., Grond, A., Zuniga, E., Barnes, S. R., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00073-z · Cited by 188
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Raper, D. M. S., Louveau, A., & Kipnis, J. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.07.001 · Cited by 184
Louveau, A., Mesquita, S. D., & Kipnis, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.08.027 · Cited by 177
Zimmerman, B., Rypma, B., Gratton, G., & Fabiani, M. (2021) · Psychophysiology · doi:10.1111/psyp.13796 · Cited by 179
Versele, R., Sevin, E., Gosselet, F., Fénart, L., & Candela, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810235 · Cited by 187
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Ubelmann, F., Burrinha, T., Salavessa, L., Gomes, R., Ferreira, C., Moreno, N., & Guimas Almeida, C. (2017) · The EMBO Reports · doi:10.15252/embr.201642738 · Cited by 165
Dourlen, P., Kilinc, D., Malmanche, N., Chapuis, J., & Lambert, J.-C. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02004-0 · Cited by 168
Smith, A. J., & Verkman, A. S. (2017) · The FASEB Journal · doi:10.1096/fj.201700999 · Cited by 162
Transcriptomic comparison of human and mouse brain microvessels
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Iadecola, C., Smith, E. E., Anrather, J., Gu, C., Mishra, A., Misra, S., Pérez‐Pinzón, M. A., Shih, A. Y., Sorond, F. A., van Veluw, S. J., et al. (2023) · Stroke · doi:10.1161/str.0000000000000431 · Cited by 161
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Pinheiro, L. M. V., & Faustino, C. M. C. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190321163438 · Cited by 144
Storck, S. E., Hartz, A. M. S., Bernard, J., Wolf, A., Kachlmeier, A., Mahringer, A., Weggen, S., Pahnke, J., & Pietrzik, C. U. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.07.017 · Cited by 143
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The genetic landscape of Alzheimer disease
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Xiao, M., Xiao, Z. J., Yang, B., Lan, Z., & Fang, F. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00764 · Cited by 119
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Guix, F. X., Sannerud, R., Berditchevski, F., Arranz, A. M., Horré, K., Snellinx, A., Thathiah, A., Saido, T. C., Saito, T., Rajesh, S., et al. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0165-0 · Cited by 103
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Gali, C. C., Fanaee‐Danesh, E., Zandl‐Lang, M., Albrecher, N. M., Tam‐Amersdorfer, C., Stracke, A., Sachdev, V., Reichmann, F., Sun, Y., Avdili, A., et al. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.103390 · Cited by 87
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Tian, X., Leite, D. M., Scarpa, E., Nyberg, S., Fullstone, G., Forth, J., Matias, D., Apriceno, A., Poma, A., Duro‐Castaño, A., et al. (2020) · Science Advances · doi:10.1126/sciadv.abc4397 · Cited by 91
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Khan, N. U., Jiang, N., Ju, X., Miao, T., Chen, H., & Han, L. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.10.015 · Cited by 83
Yang, Y., Xiong, X., Liu, J., Wu, L., Zhong, Q., Zhou, K., Meng, Z., Liu, L., Wang, F., Gong, Q., et al. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.005811 · Cited by 87
Soliman, H. M., Ghonaim, G. A., Gharib, S. M., Chopra, H., Farag, A. K., Hassanin, M. H., Nagah, A., Emad-Eldin, M., Hashem, N. E., Yahya, G., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910794 · Cited by 81
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Nelson, A. R., Sagare, A. P., & Zloković, B. V. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1711357114 · Cited by 79
Self-citation
Metadata
- Authors
- Zhao, Z., Sagare, A. P., Ma, Q., Halliday, M. R., Kong, P., Kisler, K., Winkler, E. A., Ramanathan, A., Kanekiyo, T., Bu, G., Owens, N. C., Rege, S. V., Si, G., Ahuja, A., Zhu, D., Miller, C. A., Schneider, J. A., Maeda, M., Maeda, T., Sugawara, T., Ichida, J. K., & Zlokovic, B. V.
- Affiliations
- University of Southern California (US)
- Mayo Clinic (US)
- North Carolina Agricultural and Technical State University (US)
- Rush University Medical Center (US)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2015-05-25
- Volume
- 18
- Issue
- 7
- Pages
- 978-987
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4482781
- OpenAlex
- W1516940938
- Cited by
- 410
- References
- 59
- Citations by year
- 2026: 26 · 2025: 24 · 2024: 32 · 2023: 36 · 2022: 31 · 2021: 36 · 2020: 50 · 2019: 48 · 2018: 50 · 2017: 30 · 2016: 33 · 2015: 14
- FWCI
- 31.19
- Type
- journal article
- Language
- en
- Update notices
- correction (2023-11-20)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- The Scholars Repository - LLU (Loma Linda University) (submittedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Institute on Aging (P01AG030128, R01AG039452, R01AG027924, R37AG023084, P50AG005142, RF1AG046205, R37AG23084, R01AG046205, R01AG035355, P50AG016574)
- National Institute of Neurological Disorders and Stroke (R37NS034467, R00-NS07743, R37NS34467, P01NS074969)
- 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 › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- PICALM, amyloid-beta, blood-brain barrier, transcytosis, amyloid-beta clearance, Alzheimer's disease, brain endothelium, clathrin-mediated endocytosis, LRP1, Rab5, Rab11, cognitive impairment, iPSC-derived endothelial cells, adenoviral gene transfer
- MeSH terms
- Alzheimer Disease, Animals, Blood-Brain Barrier, Capillaries, Cerebral Cortex, Endothelium, Vascular, Homeostasis, Humans, Metabolic Clearance Rate, Amyloid beta-Peptides, Mice, Knockout, Monomeric Clathrin Assembly Proteins, Pluripotent Stem Cells, Mice, Transcytosis
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