Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism
Open accessAbstract
Abstract Background Clearance at the blood-brain barrier (BBB) plays an important role in removal of Alzheimer’s amyloid-β (Aβ) toxin from brain both in humans and animal models. Apolipoprotein E (apoE), the major genetic risk factor for AD, disrupts Aβ clearance at the BBB. The cellular and molecular mechanisms, however, still remain unclear, particularly whether the BBB-associated brain capillary pericytes can contribute to removal of aggregated Aβ from brain capillaries, and whether removal of Aβ aggregates by pericytes requires apoE, and if so, is Aβ clearance on pericytes apoE isoform-specific. Methods We performed immunostaining for Aβ and pericyte biomarkers on brain capillaries (< 6 μm in diameter) on tissue sections derived from AD patients and age-matched controls, and APPSwe/0 mice and littermate controls. Human Cy3-Aβ42 uptake by pericytes was studied on freshly isolated brain slices from control mice, pericyte LRP1-deficient mice (Lrplox/lox;Cspg4-Cre) and littermate controls. Clearance of aggregated Aβ42 by mouse pericytes was studied on multi-spot glass slides under different experimental conditions including pharmacologic and/or genetic inhibition of the low density lipoprotein receptor related protein 1 (LRP1), an apoE receptor, and/or silencing mouse endogenous Apoe in the presence and absence of human astrocyte-derived lipidated apoE3 or apoE4. Student’s t-test and one-way ANOVA followed by Bonferroni's post-hoc test were used for statistical analysis. Results First, we found that 35% and 60% of brain capillary pericytes accumulate Aβ in AD patients and 8.5-month-old APPSw/0 mice, respectively, compared to negligible uptake in controls. Cy3-Aβ42 species were abundantly taken up by pericytes on cultured mouse brain slices via LRP1, as shown by both pharmacologic and genetic inhibition of LRP1 in pericytes. Mouse pericytes vigorously cleared aggregated Cy3-Aβ42 from multi-spot glass slides via LRP1, which was inhibited by pharmacologic and/or genetic knockdown of mouse endogenous apoE. Human astrocyte-derived lipidated apoE3, but not apoE4, normalized Aβ42 clearance by mouse pericytes with silenced mouse apoE. Conclusions Our data suggest that BBB-associated pericytes clear Aβ aggregates via an LRP1/apoE isoform-specific mechanism. These data support the role of LRP1/apoE interactions on pericytes as a potential therapeutic target for controlling Aβ clearance in AD.
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
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?
ApoE assists in amyloid-β clearance in an isoform-dependent manner wherein apoE2 > apoE3 > apoE4.
“ApoE assists in Aβ clearance in an isoform-dependent manner wherein apoE2 > apoE3 > apoE4 [29, 30, 59].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [59]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
2 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 · see citing works
Self-citationRetractedMontagne, 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 · see citing works
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 · see citing works
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537 · see citing works
Self-citationAmyloid 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 · see citing works
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164 · see citing works
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 · see citing works
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459 · see citing works
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 · see citing works
Self-citationNeurovascular 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 · see citing works
Self-citationPericytes regulate the blood–brain barrier
Armulik, A., Genové, G., Mäe, M., Nisancioglu, M. H., Wallgard, E., Niaudet, C., He, L., Norlin, J., Lindblom, P., Strittmatter, K., et al. (2010) · Nature · doi:10.1038/nature09522 · Cited by 2,843 · see citing works
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078 · see citing works
Clearance systems in the brain—implications for Alzheimer disease
Tarasoff-Conway, J. M., Carare, R. O., Osorio, R. S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zlokovic, B. V., et al. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.119 · Cited by 1,678 · see citing works
Self-citationEstablishment and Dysfunction of the Blood-Brain Barrier
Zhao, Z., Nelson, A. R., Betsholtz, C., & Zlokovic, B. V. (2015) · Cell · doi:10.1016/j.cell.2015.10.067 · Cited by 1,670 · see citing works
Self-citationBell, R. D., Winkler, E. A., Sagare, A. P., Singh, I., LaRue, B., Deane, R., & Zlokovic, B. V. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.043 · Cited by 1,448 · see citing works
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 · see citing works
Shibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10498 · Cited by 1,413 · see citing works
Self-citationApolipoprotein E controls cerebrovascular integrity via cyclophilin A
Bell, R. D., Winkler, E. A., Singh, I., Sagare, A. P., Deane, R., Wu, Z., Holtzman, D. M., Betsholtz, C., Armulik, A., Sallstrom, J., et al. (2012) · Nature · doi:10.1038/nature11087 · Cited by 1,293 · see citing works
Self-citationA three-dimensional human neural cell culture model of Alzheimer’s disease
Choi, S. H., Kim, Y. H., Hebisch, M., Sliwinski, C., Lee, S., D’Avanzo, C., Chen, H., Hooli, B., Asselin, C., Muffat, J., et al. (2014) · Nature · doi:10.1038/nature13800 · Cited by 1,195 · see citing works
Pericytes of the neurovascular unit: key functions and signaling pathways
Sweeney, M. D., Ayyadurai, S., & Zlokovic, B. V. (2016) · Nature Neuroscience · doi:10.1038/nn.4288 · Cited by 1,125 · see citing works
Cerebral microvascular pathology in aging and Alzheimer's disease
Farkas, E., & Luiten, P. G. M. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00068-x · Cited by 1,102 · see citing works
Adult mouse astrocytes degrade amyloid-β in vitro and in situ
Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C., & Husemann, J. (2003) · Nature Medicine · doi:10.1038/nm838 · Cited by 909 · see citing works
Apolipoprotein E in Alzheimer’s disease and other neurological disorders
Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70325-2 · Cited by 857 · see citing works
Self-citationLRP/Amyloid β-Peptide Interaction Mediates Differential Brain Efflux of Aβ Isoforms
Deane, R., Wu, Z., Sagare, A., Davis, J., Du Yan, S., Hamm, K., Xu, F., Parisi, M., LaRue, B., Hu, H. W., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.017 · Cited by 828 · see citing works
Self-citationApolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease
Holtzman, D. M., Herz, J., & Bu, G. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006312 · Cited by 782 · see citing works
Self-citationapoE isoform–specific disruption of amyloid β peptide clearance from mouse brain
Deane, R., Sagare, A., Hamm, K., Parisi, M., Lane, S., Finn, M. B., Holtzman, D. M., & Zlokovic, B. V. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36663 · Cited by 771 · see citing works
Self-citationNG2 cells generate both oligodendrocytes and gray matter astrocytes
Zhu, X., Bergles, D. E., & Nishiyama, A. (2007) · Development · doi:10.1242/dev.004895 · Cited by 678 · see citing works
Alzheimer’s disease: A matter of blood–brain barrier dysfunction?
Montagne, A., Zhao, Z., & Zlokovic, B. V. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20171406 · Cited by 672 · see citing works
Self-citationBell, R. D., Sagare, A. P., Friedman, A. E., Bedi, G. S., Holtzman, D. M., Deane, R., & Zlokovic, B. V. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600419 · Cited by 670 · see citing works
Self-citationHalliday, M. R., Rege, S. V., Ma, Q., Zhao, Z., Miller, C. A., Winkler, E. A., & Zlokovic, B. V. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.44 · Cited by 649 · see citing works
Self-citationApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?
Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608 · see citing works
Vascular contributions to cognitive impairment and dementia including Alzheimer's disease
Snyder, H. M., Corriveau, R. A., Craft, S., Faber, J. E., Greenberg, S. M., Knopman, D., Lamb, B. T., Montine, T. J., Nedergaard, M., Schaffer, C. B., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.10.008 · Cited by 603 · see citing works
Self-citationLRP: Role in Vascular Wall Integrity and Protection from Atherosclerosis
Boucher, P., Gotthardt, M., Li, W., Anderson, R. G. W., & Herz, J. (2003) · Science · doi:10.1126/science.1082095 · Cited by 581 · see citing works
Self-citationHerz, J., Goldstein, J. L., Strickland, D. K., Ho, Y. K., & Brown, M. S. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54845-6 · Cited by 576 · see citing works
Self-citationApolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides
Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., Higgs, R., Liu, F., Malkani, S., Bales, K. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1058 · Cited by 571 · see citing works
Sengillo, J. D., Winkler, E. A., Walker, C. T., Sullivan, J. S., Johnson, M., & Zlokovic, B. V. (2013) · Brain Pathology · doi:10.1111/bpa.12004 · Cited by 553 · see citing works
Self-citationPericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain
Kisler, K., Nelson, A. R., Rege, S. V., Ramanathan, A., Wang, Y., Ahuja, A., Lazic, D., Tsai, P. S., Zhao, Z., Zhou, Y., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4489 · Cited by 497 · see citing works
Self-citationEndothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier
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 · see citing works
Rohlmann, A., Gotthardt, M., Hammer, R. E., & Herz, J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1240 · Cited by 455 · see citing works
Self-citationCentral role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance
Zhao, Z., Sagare, A. P., Ma, Q., Halliday, M. R., Kong, P., Kisler, K., Winkler, E. A., Ramanathan, A., Kanekiyo, T., Bu, G., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4025 · Cited by 410 · see citing works
Self-citationVascular, glial, and lymphatic immune gateways of the central nervous system
Engelhardt, B., Carare, R. O., Bechmann, I., Flügel, A., Laman, J. D., & Weller, R. O. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1606-5 · Cited by 362 · see citing works
Bakker, E. N. T. P., Bacskai, B. J., Arbel-Ornath, M., Aldea, R., Bedussi, B., Morris, A. W. J., Weller, R. O., & Carare, R. O. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-015-0273-8 · Cited by 353 · see citing works
Fryer, J. D., Simmons, K., Parsadanian, M., Bales, K. R., Paul, S. M., Sullivan, P. M., & Holtzman, D. M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5170-04.2005 · Cited by 278 · see citing works
Self-citationCerebrovascular Effects of Apolipoprotein E: Implications for Alzheimer Disease
Zlokovic, B. V. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.2152 · Cited by 263 · see citing works
SRF and myocardin regulate LRP-mediated amyloid-β clearance in brain vascular cells
Bell, R. D., Deane, R., Chow, N., Long, X., Sagare, A., Singh, I., Streb, J. W., Guo, H., Rubio, A., Van Nostrand, W., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1819 · Cited by 261 · see citing works
Self-citationAmyloid‐β efflux from the central nervous system into the plasma
Roberts, K. F., Elbert, D. L., Kasten, T. P., Patterson, B. W., Sigurdson, W. C., Connors, R., Ovod, V., Munsell, L. Y., Mawuenyega, K. G., Miller‐Thomas, M. M., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24270 · Cited by 250 · see citing works
LRP1 in Brain Vascular Smooth Muscle Cells Mediates Local Clearance of Alzheimer's Amyloid-β
Kanekiyo, T., Liu, C., Shinohara, M., Li, J., & Bu, G. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3987-12.2012 · Cited by 221 · see citing works
Miners, J. S., Schulz, I., & Love, S. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17690761 · Cited by 208 · see citing works
Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease
Liao, F., Yoon, H., & Kim, J. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000383 · Cited by 191 · see citing works
Hultman, K., Strickland, S., & Norris, E. H. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.76 · Cited by 183 · see citing works
The vascular factor in Alzheimer's disease: A study in Golgi technique and electron microscopy
Baloyannis, S. J., & Baloyannis, I. S. (2012) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2012.07.010 · Cited by 150 · see citing works
Wilhelmus, M. M. M., Otte-Höller, I., van Triel, J. J. J., Veerhuis, R., Maat-Schieman, M. L. C., Bu, G., de Waal, R. M. W., & Verbeek, M. M. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070050 · Cited by 138 · see citing works
Morikawa, M., Fryer, J. D., Sullivan, P. M., Christopher, E., Schindler, S. E., Demattos, R. B., Odell, M., Fagan, A. M., Lashuel, H. A., Walz, T., et al. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.11.005 · Cited by 136 · see citing works
Self-citationAPOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis
Rannikmäe, K., Kalaria, R. N., Greenberg, S. M., Chui, H. C., Schmitt, F. A., Samarasekera, N., Salman, R. A., & Sudlow, C. L. M. (2013) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2013-306485 · Cited by 131 · see citing works
Innate immunity receptor CD36 promotes cerebral amyloid angiopathy
Park, L., Zhou, J., Zhou, P., Pistick, R., Jamal, S. E., Younkin, L. H., Pierce, J. P., Arreguin, A. J., Anrather, J., Younkin, S. G., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300021110 · Cited by 130 · see citing works
Impact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer’s disease
Shinohara, M., Murray, M. E., Frank, R. D., Shinohara, M., DeTure, M., Yamazaki, Y., Tachibana, M., Atagi, Y., Davis, M. D., Liu, C.-C., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1580-y · Cited by 123 · see citing works
A simple method for isolation and characterization of mouse brain microvascular endothelial cells
Wu, Z., Hofman, F. M., & Zloković, B. V. (2003) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(03)00206-1 · Cited by 114 · see citing works
Self-citationThe growing clinical spectrum of cerebral amyloid angiopathy
Wermer, M. J. H., & Greenberg, S. M. (2017) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000510 · Cited by 111 · see citing works
The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice
Cacciottolo, M., Christensen, A., Moser, V. A., Liu, J., Pike, C. J., Smith, C. C., LaDu, M. J., Sullivan, P. M., Morgan, T. E., Dolzhenko, E., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.10.010 · Cited by 94 · see citing works
Tachibana, M., Yamazaki, Y., Liu, C., Bu, G., & Kanekiyo, T. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.10.023 · Cited by 92 · see citing works
Hecht, M., Krämer, L. M., Arnim, C., Otto, M., & Thal, D. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1834-y · Cited by 92 · see citing works
Mechanism of Neuronal versus Endothelial Cell Uptake of Alzheimer's Disease Amyloid β Protein
Kandimalla, K. K., Scott, O. G., Fulzele, S., Davidson, M. W., & Poduslo, J. F. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004627 · Cited by 88 · see citing works
Prevalence of cortical superficial siderosis in a memory clinic population
Zonneveld, H. I., Goos, J. D. C., Wattjes, M. P., Prins, N. D., Scheltens, P., van der Flier, W. M., Kuijer, J. P. A., Muller, M., & Barkhof, F. (2014) · Neurology · doi:10.1212/wnl.0000000000000150 · Cited by 78 · see citing works
Webster, C. I., Burrell, M. R., Olsson, L., Fowler, S. A., Digby, S., Sandercock, A. M., Snijder, A., Tebbe, J., Haupts, U. M., Grudzinska, J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104001 · Cited by 73 · see citing works
Apolipoprotein E protects cultured pericytes and astrocytes from D-Aβ1–40-mediated cell death
Bruinsma, I. B., Wilhelmus, M. M. M., Kox, M., Veerhuis, R., de Waal, R. M. W., & Verbeek, M. M. (2009) · Brain Research · doi:10.1016/j.brainres.2009.12.039 · Cited by 58 · see citing works
Verbeek, M. M., Nostrand, W. E. V., Otte‐Höller, I., Wesseling, P., & de Waal, R. M. W. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06368.x · Cited by 55 · see citing works
Apolipoprotein E Genotype Regulates Amyloid-β Cytotoxicity
Wilhelmus, M. M. M., Otte‐Höller, I., Davis, J., Nostrand, W. E. V., de Waal, R. M. W., & Verbeek, M. M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4213-04.2005 · Cited by 54 · see citing works
Esiri, M. M., Joachim, C., Sloan, C., Christie, S., Agacinski, G., Bridges, L. R., Wilcock, G. K., & Smith, A. D. (2014) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31829b72f1 · Cited by 42 · see citing works
A lymphatic waste-disposal system implicated in Alzheimer’s disease
Sweeney, M. D., & Zloković, B. V. (2018) · Nature · doi:10.1038/d41586-018-05763-0 · Cited by 35 · see citing works
Self-citationAβ-degrading proteases:therapeutic potential in Alzheimer disease
Leissring, M. (2016) · CNS Drugs · doi:10.1007/s40263-016-0364-1 · Cited by 25 · see citing works
Cluster: barriers of the central nervous system
Engelhardt, B. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1816-0 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425 · see citing works
APOE and Alzheimer’s disease: Advances in genetics, pathophysiology, and therapeutic approaches
Serrano-Pozo, A., Das, S., & Hyman, B. T. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30412-9 · Cited by 1,037 · see citing works
ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies
Raulin, A.-C., Doss, S. V., Trottier, Z. A., Ikezu, T. C., Bu, G., & Liu, C.-C. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00574-4 · Cited by 756 · see citing works
Pericytes and Neurovascular Function in the Healthy and Diseased Brain
Brown, L. S., Foster, C. G., Courtney, J.-M., King, N. E., Howells, D. W., & Sutherland, B. A. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00282 · Cited by 406 · see citing works
Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss
Nikolakopoulou, A. M., Montagne, A., Kisler, K., Dai, Z., Wang, Y., Huuskonen, M. T., Sagare, A. P., Lazić, D., Sweeney, M. D., Kong, P., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0434-z · Cited by 382 · see citing works
Self-citationAPOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics
Husain, M. A., Laurent, B., & Plourde, M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.630502 · Cited by 353 · see citing works
APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
Li, Z., Shue, F., Zhao, N., Shinohara, M., & Bu, G. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00413-4 · Cited by 306 · see citing works
The neuroimmune axis of Alzheimer’s disease
Jorfi, M., Maaser‐Hecker, A., & Tanzi, R. E. (2023) · Genome Medicine · doi:10.1186/s13073-023-01155-w · Cited by 299 · see citing works
Challenges and hopes for Alzheimer’s disease
Tatulian, S. A. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.01.016 · Cited by 291 · see citing works
Factors influencing the blood-brain barrier permeability
Zhao, Y., Gan, L., Ren, L., Lin, Y., Ma, C., & Lin, X. (2022) · Brain Research · doi:10.1016/j.brainres.2022.147937 · Cited by 291 · see citing works
Restoring Wnt/β-catenin signaling is a promising therapeutic strategy for Alzheimer’s disease
Jia, L., Piña-Crespo, J., & Li, Y. (2019) · Molecular Brain · doi:10.1186/s13041-019-0525-5 · Cited by 288 · see citing works
Fernández-Calle, R., Konings, S. C., Frontiñán-Rubio, J., García-Revilla, J., Camprubí-Ferrer, L., Svensson, M., Martinson, I., Boza-Serrano, A., Venero, J. L., Nielsen, H. M., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00566-4 · Cited by 278 · see citing works
Fernandez, C. G., Hamby, M. E., McReynolds, M. L., & Ray, W. J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00014 · Cited by 277 · see citing works
Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia
Uemura, M. T., Maki, T., Ihara, M., Lee, V. M. ‐., & Trojanowski, J. Q. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00080 · Cited by 239 · see citing works
Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina
Shi, H., Koronyo, Y., Rentsendorj, A., Regis, G. C., Sheyn, J., Fuchs, D.-T., Kramerov, A. A., Ljubimov, A. V., Dumitrascu, O. M., Rodriguez, A. R., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02134-w · Cited by 230 · see citing works
Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: impact of genetic risk factors
Van Acker, Z. P., Bretou, M., & Annaert, W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0323-7 · Cited by 222 · see citing works
A Historical Review of Brain Drug Delivery
Pardridge, W. M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061283 · Cited by 219 · see citing works
Blood–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 · see citing works
Relationship Between Amyloid-β Deposition and Blood–Brain Barrier Dysfunction in Alzheimer’s Disease
Wang, D., Chen, F., Han, Z., Yin, Z., Ge, X., & Lei, P. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.695479 · Cited by 201 · see citing works
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease
Najm, R., Jones, E. A., & Huang, Y. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0324-6 · Cited by 183 · see citing works
Dysfunction of the blood–brain barrier in Alzheimer's disease: Evidence from human studies
Kurz, C., Walker, L., Rauchmann, B., & Perneczky, R. (2022) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12782 · Cited by 183 · see citing works
“permeability and cerebral blood flow but are also involved in the clearance of Aβ.(60) Hallmarks of AD pathology (Aβ load, Braak stages) and the extent of BBB damage were positively associated with expression of the vasoactive mediator (vasoconstrictor) endothelin.”
BackgroundGouveia-Freitas, K., & de Bastos-Leite, A. J. (2021) · Neuroradiology · doi:10.1007/s00234-021-02718-7 · Cited by 161 · see citing works
Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes
Lendahl, U., Nilsson, P., & Betsholtz, C. (2019) · EMBO Reports · doi:10.15252/embr.201948070 · Cited by 141 · see citing works
The Neurovascular Unit Dysfunction in Alzheimer’s Disease
Soto-Rojas, L. O., Pacheco‐Herrero, M., Martínez-Gómez, P. A., Campa-Córdoba, B. B., Apátiga-Pérez, R., Villegas-Rojas, M. M., Harrington, C. R., de la Cruz, F., Garcés‐Ramírez, L., & Luna‐Muñoz, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042022 · Cited by 140 · see citing works
Bioengineering methods for vascularizing organoids
Nwokoye, P. N., & Abilez, O. J. (2024) · Cell Reports Methods · doi:10.1016/j.crmeth.2024.100779 · Cited by 142 · see citing works
Pathological changes within the cerebral vasculature in Alzheimer’s disease: New perspectives
Fisher, R. A., Miners, J. S., & Love, S. (2022) · Brain Pathology · doi:10.1111/bpa.13061 · Cited by 127 · see citing works
Blood-brain barrier integrity in the pathogenesis of Alzheimer’s disease
Huang, Z., Wong, L., Su, Y., Huang, X., Wang, N., Chen, H., & Yi, C. (2020) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2020.100857 · Cited by 130 · see citing works
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 118 · see citing works
The role of the blood–brain barrier during neurological disease and infection
Patabendige, A., & Janigro, D. (2023) · Biochemical Society Transactions · doi:10.1042/bst20220830 · Cited by 119 · see citing works
The role of endothelial cell–pericyte interactions in vascularization and diseases
Li, G., Gao, J., Ding, P., & Gao, Y. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.01.016 · Cited by 125 · see citing works
Van Gool, B., Storck, S. E., Reekmans, S. M., Lechat, B., Gordts, P. L. S. M., Pradier, L., Pietrzik, C. U., & Roebroek, A. J. M. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-1594-2 · Cited by 114 · see citing works
The contribution of glial cells to Huntington's disease pathogenesis
Wilton, D. K., & Stevens, B. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104963 · Cited by 112 · see citing works
Xiao, M., Xiao, Z. J., Yang, B., Lan, Z., & Fang, F. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00764 · Cited by 113 · see citing works
The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment
Lv, T., Zhao, B., Hu, Q., & Zhang, X. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.689098 · Cited by 105 · see citing works
Glia in neurodegeneration: Drivers of disease or along for the ride?
Gleichman, A. J., & Carmichael, S. T. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104957 · Cited by 90 · see citing works
The Role of Neurovascular System in Neurodegenerative Diseases
Ahmad, A., Patel, V., Xiao, J., & Khan, M. M. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02023-z · Cited by 94 · see citing works
Roles of ApoE4 on the Pathogenesis in Alzheimer’s Disease and the Potential Therapeutic Approaches
Sun, Y.-Y., Wang, Z., & Huang, H. (2023) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-023-01365-1 · Cited by 95 · see citing works
Blood–Brain Barrier and Neurodegenerative Diseases—Modeling with iPSC-Derived Brain Cells
Wu, Y., Sonninen, T.-M., Peltonen, S., Koıstınaho, J., & Lehtonen, Š. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147710 · Cited by 88 · see citing works
Self-citationNeurovascular dysfunction and vascular amyloid accumulation as early events in Alzheimer's disease
Apátiga-Pérez, R., Soto-Rojas, L. O., Campa-Córdoba, B. B., Luna‐Viramontes, N. I., Cuevas, E., Villanueva‐Fierro, I., Ontiveros‐Torres, M. Á., Bravo-Muñoz, M., Flores-Rodríguez, P., Garcés‐Ramírez, L., et al. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00814-4 · Cited by 90 · see citing works
Alzheimer’s disease and its treatment–yesterday, today, and tomorrow
Kim, A. Y., Jerdi, S. A., MacDonald, R., & Triggle, C. R. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1399121 · Cited by 93 · see citing works
Friend, Foe or Both? Immune Activity in Alzheimer’s Disease
Frost, G. R., Jonas, L. A., & Li, Y. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00337 · Cited by 86 · see citing works
Brain injury-induced dysfunction of the blood brain barrier as a risk for dementia
Abrahamson, E. E., & Ikonomović, M. D. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113257 · Cited by 87 · see citing works
Apolipoprotein E4 and meningeal lymphatics in Alzheimer disease: a conceptual framework
Mentis, A. A., Dardiotis, E., & Chrousos, G. P. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0731-7 · Cited by 82 · see citing works
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 90 · see citing works
The roles of microglia and astrocytes in neuroinflammation of Alzheimer’s disease
Han, J., Zhang, Z., Zhang, P., Yu, Q., Cheng, Q., Lu, Z., & Zong, S. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1575453 · Cited by 87 · see citing works
Age-Related Functional and Expressional Changes in Efflux Pathways at the Blood-Brain Barrier
Erdő, F., & Krajcsi, P. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00196 · Cited by 77 · see citing works
Divecha, Y. A., Rampes, S., Tromp, S., Boyanova, S., Fleckney, A. L., Fidanboylu, M., & Thomas, S. A. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100052 · Cited by 79 · see citing works
Wang, J., Fan, D., Li, H.-Y., He, C.-Y., Shen, Y., Zeng, G., Chen, D., Yi, X., Ma, Y., Yu, J., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00512-w · Cited by 76 · see citing works
Lu, M., Ji, W., Chen, H., Sun, Y., Zhao, X., Wang, F., Shi, Y., Hu, Y.-N., Liu, B.-X., Wu, J., et al. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.650103 · Cited by 71 · see citing works
Self-citationPonce-Lopez, T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26094209 · Cited by 75 · see citing works
Chernick, D., Ortiz-Valle, S., Jeong, A., Qu, W., & Li, L. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134306 · Cited by 54 · see citing works
A Practical Guide to the Automated Analysis of Vascular Growth, Maturation and Injury in the Brain
Rust, R., Kirabali, T., Grönnert, L., Doğançay, B., Limasale, Y. D. P., Meinhardt, A., Werner, C., Laviña, B., Kulic, L., Nitsch, R. M., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00244 · Cited by 62 · see citing works
Preis, L., Villringer, K., Brosseron, F., Düzel, E., Jessen, F., Petzold, G. C., Ramı́rez, A., Spottke, A. E., Fiebach, J. B., & Peters, O. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01529-1 · Cited by 71 · see citing works
Receptor-mediated drug delivery of bispecific therapeutic antibodies through the blood-brain barrier
Pardridge, W. M. (2023) · Frontiers in Drug Delivery · doi:10.3389/fddev.2023.1227816 · Cited by 62 · see citing works
The Expanding Cell Diversity of the Brain Vasculature
Ross, J. M., Kim, C. N., Allen, D. E., Crouch, E. E., Narsinh, K. H., Cooke, D. L., Abla, A. A., Nowakowski, T. J., & Winkler, E. A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.600767 · Cited by 59 · see citing works
Natural Phenolic Compounds with Neuroprotective Effects
Tavan, M., Hanachi, P., Cádiz‐Gurrea, M. D. L. L., Segura‐Carretero, A., & Mirjalili, M. H. (2023) · Neurochemical Research · doi:10.1007/s11064-023-04046-z · Cited by 62 · see citing works
A New Hypothesis for Alzheimer’s Disease: The Lipid Invasion Model
Rudge, J. D. (2022) · Journal of Alzheimer's Disease Reports · doi:10.3233/adr-210299 · Cited by 58 · see citing works
The Emerging Role of Pericyte-Derived Extracellular Vesicles in Vascular and Neurological Health
Sharma, K., Zhang, Y., Paudel, K. R., Kachelmeier, A., Hansbro, P. M., & Shi, X. (2022) · Cells · doi:10.3390/cells11193108 · Cited by 58 · see citing works
Liang, X., Fa, W., Wang, N., Peng, Y., Liu, C., Zhu, M., Tian, N., Wang, Y., Han, X., Qiu, C., et al. (2022) · Aging Cell · doi:10.1111/acel.13748 · Cited by 59 · see citing works
Hubin, E., Verghese, P. B., van Nuland, N., & Broersen, K. (2019) · FEBS Letters · doi:10.1002/1873-3468.13428 · Cited by 73 · see citing works
Self-citationIn Vivo Chimeric Alzheimer’s Disease Modeling of Apolipoprotein E4 Toxicity in Human Neurons
Najm, R., Zalocusky, K. A., Zilberter, M., Yoon, S. Y., Hao, Y., Koutsodendris, N., Nelson, M., Rao, A., Taubes, A., Jones, E. A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107962 · Cited by 52 · see citing works
Research developments in the neurovascular unit and the blood‑brain barrier (Review)
Gong, Y., Wu, M., Huang, Y., He, X., Yuan, J., & Dang, B. (2025) · Biomedical Reports · doi:10.3892/br.2025.1966 · Cited by 53 · see citing works
Miners, J. S., Hulle, C. V., Ince, S., Jonaitis, E., Okonkwo, O., Bendlin, B. B., Johnson, S. C., Carlsson, C. M., Asthana, S., Love, S., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-023-02706-w · Cited by 53 · see citing works
He, Z., Wang, G., Wu, J., Tang, Z., & Luo, M. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111667 · Cited by 49 · see citing works
Alzheimer’s disease pathogenesis: standing at the crossroad of lipid metabolism and immune response
Wang, Z., Zhang, L., & Qin, C. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00857-6 · Cited by 54 · see citing works
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 47 · see citing works
Schreiber, S., Wilisch-Neumann, A., Schreiber, F., Assmann, A., Scheumann, V., Perosa, V., Jandke, S., Mawrin, C., Carare, R. O., & Werring, D. J. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12576 · Cited by 49 · see citing works
Neurodevelopmental Clues to Neurodegeneration
Schor, N. F., & Bianchi, D. W. (2021) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2021.07.012 · Cited by 48 · see citing works
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 47 · see citing works
Pericytes in Cerebrovascular Diseases: An Emerging Therapeutic Target
Su, X., Huang, L., Qu, Y., Xiao, D., & Mu, D. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00519 · Cited by 44 · see citing works
Jia, Y., Wang, N., Zhang, Y., Xue, D., Lou, H., & Liu, X. (2020) · Aging and Disease · doi:10.14336/ad.2019.0519 · Cited by 45 · see citing works
Alcendor, D. J. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9051490 · Cited by 47 · see citing works
Pericytes: Problems and Promises for CNS Repair
Laredo, F., Plebanski, J., & Tedeschi, A. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00546 · Cited by 44 · see citing works
Lv, X., Zhang, M., Cheng, Z., Wang, Q., Wang, P., Xie, Q., Ni, M., Shen, Y., Tang, Q., & Gao, F. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01199-5 · Cited by 44 · see citing works
The retina: A window in which to view the pathogenesis of Alzheimer’s disease
Zhang, J., Shi, L., & Shen, Y. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101590 · Cited by 43 · see citing works
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 45 · see citing works
Emerging role of HDL in brain cholesterol metabolism and neurodegenerative disorders
Turri, M., Marchi, C., Adorni, M. P., Calabresi, L., & Zimetti, F. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2022.159123 · Cited by 54 · see citing works
McMillan, I. O., Li, J., & Wang, L. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00247.2022 · Cited by 42 · see citing works
Advanced Human BBB‐on‐a‐Chip: A New Platform for Alzheimer's Disease Studies
Yoon, J., Kim, J., Shah, Z., Awasthi, A., Mahajan, A., & Kim, Y. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202002285 · Cited by 44 · see citing works
ApoE4-Mediated Blood Brain Barrier Damage in Alzheimer's Disease: Progress and Prospects
Zhou, X., Shi, Q., Zhang, X., Gu, L., Li, J., Ju, Y., Hu, M., Zhao, X., & Li, Q. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.110670 · Cited by 37 · see citing works
Kirabali, T., Rigotti, S., Siccoli, A., Liebsch, F., Shobo, A., Höck, C., Nitsch, R. M., Multhaup, G., & Kulic, L. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0846-8 · Cited by 43 · see citing works
Amyloid β oligomer induces cerebral vasculopathy via pericyte-mediated endothelial dysfunction
Chen, S., Guo, D., Zhu, Y., Xiao, S., Xie, J., Zhang, Z., Hu, Y., Huang, J., Ma, X., Ning, Z., et al. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01423-w · Cited by 41 · see citing works
Dalkara, T. (2019) · Stroke · doi:10.1161/strokeaha.118.023590 · Cited by 40 · see citing works
Denser brain capillary network with preserved pericytes in Alzheimer's disease
Fernández‐Klett, F., Brandt, L., Fernández‐Zapata, C., Abuelnor, B., Middeldorp, J., Sluijs, J. A., Curtis, M. A., Faull, R. L. M., Harris, L. W., Bahn, S., et al. (2020) · Brain Pathology · doi:10.1111/bpa.12897 · Cited by 39 · see citing works
Kirchner, K., Garvert, L., Kühn, A. L., Bonk, S., Grabe, H. J., & der Auwera, S. V. (2023) · Cells · doi:10.3390/cells12212512 · Cited by 39 · see citing works
The vascular contribution of apolipoprotein E to Alzheimer’s disease
Chen, F., Zhao, J., Meng, F., He, F., Ni, J., & Fu, Y. (2024) · Brain · doi:10.1093/brain/awae156 · Cited by 38 · see citing works
Multi-functional role of apolipoprotein E in neurodegenerative diseases
Islam, S., Noorani, A., Sun, Y., Michikawa, M., & Zou, K. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1535280 · Cited by 30 · see citing works
The role of ApoE-mediated microglial lipid metabolism in brain aging and disease
Yen, J.-H. J., & Yu, I.-C. I. (2023) · Immunometabolism · doi:10.1097/in9.0000000000000018 · Cited by 37 · see citing works
Padovani, A., Galli, A., Bazzoli, E., Tolassi, C., Caratozzolo, S., Gumina, B., Benussi, A., Libri, I., Outeiro, T. F., & Pilotto, A. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14556 · Cited by 37 · see citing works
Pardridge, W. M. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114234 · Cited by 37 · see citing works
The Multiple Roles of Pericytes in Vascular Formation and Microglial Functions in the Brain
Hattori, Y. (2022) · Life · doi:10.3390/life12111835 · Cited by 37 · see citing works
Blood–Brain Barrier ( BBB ) Dysfunction in CNS Diseases: Paying Attention to Pericytes
Yu, T., Wang, Z., Chen, Y., Xiang, Y., Wu, M., Zhang, M., Yin, X., & Chen, Z. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70422 · Cited by 36 · see citing works
Bohannon, D. G., Long, D., & Kim, W. (2021) · Cells · doi:10.3390/cells10040890 · Cited by 34 · see citing works
Suppression of Fli-1 protects against pericyte loss and cognitive deficits in Alzheimer's disease
Li, P., Wu, Y., Hamlett, E. D., Goodwin, A. J., Halushka, P. V., Carroll, S. L., Liu, M., & Fan, H. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.01.023 · Cited by 33 · see citing works
Self-citationMahaman, Y. A. R., Huang, F., Salissou, M. T. M., Yacouba, M. B. M., Wang, J., Liu, R., Zhang, B., Li, H., Zhu, F., & Wang, X. (2023) · Neurotherapeutics · doi:10.1007/s13311-023-01356-6 · Cited by 33 · see citing works
In vivo self-assembled drug nanocrystals for metastatic breast cancer all-stage targeted therapy
Luo, Z., Lu, L., Xu, W., Meng, N., Wu, S., Zhou, J., Xu, Q., Xie, C., Liu, Y., & Lu, W. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.03.058 · Cited by 32 · see citing works
On the Common Journey of Neural Cells through Ischemic Brain Injury and Alzheimer’s Disease
Kriška, J., Heřmanová, Z., Knotek, T., Turečková, J., & Anděrová, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189689 · Cited by 33 · see citing works
Engineering Brain-Specific Pericytes from Human Pluripotent Stem Cells
Jeske, R., Albo, J., Marzano, M., Bejoy, J., & Li, Y. (2020) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2020.0091 · Cited by 30 · see citing works
Tarawneh, R. (2023) · Biomolecules · doi:10.3390/biom13050830 · Cited by 29 · see citing works
Elahi, F. M., Ashimatey, B. S., Bennett, D. J., Walters, S. M., Joie, R. L., Jiang, X., Wolf, A. A., Cobigo, Y., Staffaroni, A. M., Rosen, H. J., et al. (2021) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12181 · Cited by 29 · see citing works
- Authors
- 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.
- Affiliations
- University of Southern California (US)
- C2N Diagnostics (United States) (US)
- The University of Texas Southwestern Medical Center (US)
- Washington University in St. Louis (US)
- Venue
- Molecular Neurodegeneration
- Published
- 2018-10-19
- Volume
- 13
- Issue
- 1
- Pages
- 57-57
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC6194676
- OpenAlex
- W2897433925
- Cited by
- 281
- References
- 71
- Citations by year
- 2026: 24 · 2025: 54 · 2024: 40 · 2023: 41 · 2022: 35 · 2021: 30 · 2020: 36 · 2019: 21
- FWCI
- 14.91
- Type
- journal article
- Language
- en
- Update notices
- Open access
- gold
- doi.org
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- The Scholars Repository - LLU (Loma Linda University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01NS034467, R01AG023084, R01AG039452)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- blood-brain barrier, amyloid-beta 42, LRP1, apolipoprotein E isoforms, APOE3, APOE ε4, Alzheimer's disease, amyloid-beta clearance, receptor-mediated uptake, pericyte dysfunction, APP overexpression
- MeSH terms
- Animals, Apolipoproteins E, Biological Transport, Blood-Brain Barrier, Brain, Humans, Mice, Transgenic, Peptide Fragments, Receptors, LDL, Amyloid beta-Peptides, Pericytes, Tumor Suppressor Proteins, Low Density Lipoprotein Receptor-Related Protein-1
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
