Clearing amyloid through the blood-brain barrier
Open accessAbstract
According to the amyloid hypothesis, accumulation of amyloid beta-peptide (A beta) in the brain is the primary pathogenic event in Alzheimer's disease (AD). Recent evidence indicates that A beta within the intravascular space is linked to A beta deposited in the brain suggesting that transport of A beta between the brain, blood and cerebrospinal fluid, and across the blood-brain barrier, regulates brain A beta. Thus, understanding A beta exchanges between brain and blood, and vice versa, and developing transport-based systemic A beta-lowering strategies may provide new important insights into pathogenesis and therapeutic control of AD.
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Cites
The 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
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291 · see citing works
Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876 · cited 1× · see citing works
“The mechanisms responsible for Ab production, i.e. the proteolytic enzymes c- and b-secretases which generate Ab from its larger precursor protein (amyloid b-peptide precursor protein, APP), have been characterized (Selkoe 1998; Vassar et al. 1999).”
BackgroundRAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain
Deane, R., Du Yan, S., Submamaryan, R. K., LaRue, B., Jovanovic, S., Hogg, E., Welch, D., Manness, L., Lin, C., Yu, J., et al. (2003) · Nature Medicine · doi:10.1038/nm890 · Cited by 1,426 · see citing works
Self-citationShibata, 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-citationKawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00372.2001 · Cited by 1,053 · cited 1× · see citing works
“High plasma levels of Ab40 and Ab42 have been determined in mouse models of AD under basal conditions, e.g. Tg-2576 mice (Kawarabayashi et al. 2001) or after treatment with Ab-peripheral binding agents, e.g. anti-Ab antibodies (DeMattos et al. 2002a), sRAGE (Deane et al. 2003).”
BackgroundMetabolic Regulation of Brain Aβ by Neprilysin
Iwata, N., Tsubuki, S., Takaki, Y., Shirotani, K., Lu, B., Gerard, N., Gerard, C., Hama, E., Lee, H., & Saido, T. (2001) · Science · doi:10.1126/science.1059946 · Cited by 894 · see citing works
The cell biology of β-amyloid precursor protein and presenilin in Alzheimer's disease
Selkoe, D. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01363-4 · Cited by 862 · see citing works
DeMattos, R. B., Bales, K. R., Cummins, D. J., Paul, S. M., & Holtzman, D. M. (2002) · Science · doi:10.1126/science.1067568 · Cited by 563 · see citing works
Clearing the brain's amyloid cobwebs
Selkoe, D. J. (2001) · Neuron · doi:10.1016/s0896-6273(01)00475-5 · Cited by 541 · see citing works
Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis
Pepys, M. B., Herbert, J., Hutchinson, W. L., Tennent, G. A., Lachmann, H. J., Gallimore, J. R., Lovat, L. B., Bartfai, T., Alanine, A., Hertel, C., et al. (2002) · Nature · doi:10.1038/417254a · Cited by 540 · see citing works
Structural and functional aspects of the blood-brain barrier
Begley, D. J., & Brightman, M. (2003) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8049-7_2 · Cited by 452 · see citing works
Serum insulin-like growth factor I regulates brain amyloid-β levels
Carro, E., Trejo, J. L., Gómez‐Isla, T., LeRoith, D., & Torres‐Alemán, I. (2002) · Nature Medicine · doi:10.1038/nm793 · Cited by 448 · see citing works
Serum insulin-like growth factor I regulates brain amyloid-β levels
Carro, E., Jl, T., Gómez‐Isla, T., LeRoith, D., & Torres‐Alemán, I. (2002) · Nature Medicine · doi:10.1038/nm1202-793 · Cited by 442 · see citing works
Zlokovic, B. V., Martel, C. L., Matsubara, E., McComb, J. G., Zheng, G., McCluskey, R. T., Frangione, B., & Ghiso, J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.4229 · Cited by 430 · see citing works
Self-citationSilverberg, G., Mayo, M., Saul, T., Rubenstein, E., & Mcguire, D. (2003) · Lancet Neurology · doi:10.1016/s1474-4422(03)00487-3 · Cited by 429 · see citing works
β‐Amyloid efflux mediated by p‐glycoprotein
Lam, F. C., Liu, R., Lu, P., Shapiro, A. B., Renoir, J., Sharom, F. J., & Reiner, P. B. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00113.x · Cited by 379 · see citing works
Vogelgesang, S., Cascorbi, I., Schroeder, E., Pahnke, J., Kroemer, H. K., Siegmund, W., Kunert‐Keil, C., Walker, L. C., & Warzok, R. (2002) · Pharmacogenetics · doi:10.1097/00008571-200210000-00005 · Cited by 344 · see citing works
Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis
Yan, S. D., Zhu, H., Zhu, A., Golabek, A., Du, H., Roher, A., Yu, J., Soto, C., Schmidt, A. M., Stern, D., et al. (2000) · Nature Medicine · doi:10.1038/76216 · Cited by 343 · see citing works
Matsuoka, Y., Saito, M., LaFrancois, J. J., Saito, M., Gaynor, K., Olm, V., Wang, L., Casey, E., Lu, Y., Shiratori, C., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00029.2003 · Cited by 324 · see citing works
Kang, D. E., Saitoh, T., Chen, X., Xia, Y., Masliah, E., Hansen, L. A., Thomas, R. G., Thal, L. J., & Katzman, R. (1997) · Neurology · doi:10.1212/wnl.49.1.56 · Cited by 298 · see citing works
Sigurdsson, E. M., Scholtzova, H., Mehta, P. D., Frangione, B., & Wısnıewskı, T. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61715-4 · Cited by 258 · see citing works
Demattos, R. B., Bales, K. R., Parsadanian, M., O'Dell, M. A., Foss, E. M., Paul, S. M., & Holtzman, D. M. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00889.x · Cited by 253 · see citing works
Pietrzik, C. U., Busse, T., Merriam, D. E., Weggen, S., & Koo, E. H. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf568 · Cited by 198 · see citing works
Amyloidosis and Alzheimer’s disease
Ghiso, J. A., & Frangione, B. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00149-7 · Cited by 189 · see citing works
High Levels of Circulating Aβ42 Are Sequestered by Plasma Proteins in Alzheimer's Disease
Kuo, Y., Emmerling, M. R., Lampert, H. C., Hempelman, S. R., Kokjohn, T. A., Woods, A. S., Cotter, R. J., & Roher, A. E. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0552 · Cited by 182 · see citing works
Mačkić, J. B., Bading, J. R., Ghiso, J. A., Walker, L. C., Wısnıewskı, T., Frangione, B., & Zloković, B. V. (2002) · Vascular Pharmacology · doi:10.1016/s1537-1891(02)00198-2 · Cited by 141 · see citing works
Monro, O. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00317-7 · Cited by 107 · see citing works
Bading, J., Yamada, S., Mackic, J., Kirkman, L., Miller, C., Calero, M., Ghiso, J., Frangione, B., & Zlokovic, B. (2002) · Journal of drug targeting (Print) · doi:10.1080/10611860290031831 · Cited by 89 · see citing works
Self-citationUden, E. V., Mallory, M. E., Veinbergs, I., Alford, M. F., Rockenstein, E. M., & Masliah, E. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-21-09298.2002 · Cited by 88 · see citing works
Coaxing the LDL Receptor Family into the Fold
Herz, J., & Marschang, P. (2003) · Cell · doi:10.1016/s0092-8674(03)00073-4 · Cited by 73 · see citing works
Seiler, N., Duranton, B., Raul, F., Hong, Z., Cameron, C. E., Hu, J., Krieger, C., Schenk, J. O., Prókai, L., Horrobin, D. F., et al. (2002) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8171-5 · Cited by 34 · see citing works
Amyloidosis in Alzheimer's disease
Allsop, D., & Williams, C. H. (1994) · Biochemical Society Transactions · doi:10.1042/bst0220171 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
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A review on Alzheimer's disease pathophysiology and its management: an update
Kumar, A., Singh, A., & Ekavali (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2014.09.004 · Cited by 1,578 · see citing works
Delivery of therapeutic agents to the central nervous system: the problems and the possibilities
Begley, D. J. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.08.001 · Cited by 679 · see citing works
Alzheimer's Disease: From Pathology to Therapeutic Approaches
Jakob‐Roetne, R., & Jacobsen, H. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200802808 · Cited by 626 · see citing works
The impact of microglial activation on blood-brain barrier in brain diseases
da Fonseca, A. C. C., Matias, D., Garcia, C., Amaral, R., Geraldo, L. H., Freitas, C., & Lima, F. R. S. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00362 · Cited by 572 · see citing works
Deane, R., Wu, Z., & Zlokovic, B. V. (2004) · Stroke · doi:10.1161/01.str.0000143452.85382.d1 · Cited by 392 · see citing works
Jaeger, L. B., Dohgu, S., Sultana, R., Lynch, J. L., Owen, J. B., Erickson, M. A., Shah, G. N., Price, T. O., Fleegal-Demotta, M. A., Butterfiled, D. A., et al. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.01.017 · Cited by 281 · see citing works
Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease
Meyer, E. P., Ulmann-Schuler, A., Staufenbiel, M., & Krucker, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709788105 · Cited by 260 · see citing works
A Dynamic Relationship between Intracellular and Extracellular Pools of Aβ
Oddo, S., Caccamo, A., Smith, I. F., Green, K. N., & LaFerla, F. M. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.050593 · Cited by 261 · see citing works
The Choroid Plexus in Healthy and Diseased Brain
Kaur, C., Rathnasamy, G., & Ling, E.-A. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlv030 · Cited by 176 · see citing works
Sadowski, M. J., Pankiewicz, J., Scholtzova, H., Mehta, P. D., Prelli, F., Quartermain, D., & Wisniewski, T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604011103 · Cited by 167 · see citing works
Ocular changes in TgF344-AD rat model of Alzheimer's disease
Tsai, Y., Lu, B., Ljubimov, A. V., Girman, S., Ross-Cisneros, F. N., Sadun, A. A., Svendsen, C. N., Cohen, R. M., & Wang, S. (2014) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.13-12888 · Cited by 153 · 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
Chen, K., Maley, J., & Yu, P. H. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04181.x · Cited by 131 · see citing works
Disease modifying therapy for AD?<sup>1</sup>
Golde, T. E. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04211.x · Cited by 117 · see citing works
Serum albumin and beta-amyloid deposition in the human brain
Kim, J. W., Byun, M. S., Lee, J. H., Yi, D., Jeon, S. Y., Sohn, B. K., Lee, J.-Y., Shin, S. A., Kim, Y. K., Kang, K. M., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000010005 · Cited by 87 · see citing works
Boada, M., Anaya, F., Ortiz, P., Olazarán, J., Shua-Haim, J. R., Obisesan, T. O., Hernández, I., Muñoz, J., Buendia, M., Alegret, M., et al. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160565 · Cited by 94 · see citing works
Soluble adhesion molecules and angiotensin-converting enzyme in dementia
Nielsen, H. M., Londos, E., Minthon, L., & Janciauskiene, S. M. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.11.011 · Cited by 80 · see citing works
Ullah, R., Park, T. J., Huang, X., & Kim, M. O. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101451 · Cited by 78 · see citing works
Katsouri, L., & Georgopoulos, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021880 · Cited by 72 · see citing works
The generation and function of soluble apoE receptors in the CNS
Rebeck, G. W., LaDu, M. J., Estus, S., Bu, G., & Weeber, E. J. (2006) · Molecular Neurodegeneration · doi:10.1186/1750-1326-1-15 · Cited by 66 · see citing works
Merino-Zamorano, C., Fernández-de Retana, S., Montañola, A., Batlle, A., Saint-Pol, J., Mysiorek, C., Gosselet, F., Montaner, J., & Hernández-Guillamon, M. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150976 · Cited by 63 · see citing works
Aging alters mRNA expression of amyloid transporter genes at the blood-brain barrier
Osgood, D., Miller, M. C., Messier, A. A., Gonzalez, L., & Silverberg, G. D. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.05.011 · Cited by 63 · see citing works
Matsumoto, K., Chiba, Y., Fujihara, R., Kubo, H., Sakamoto, H., & Ueno, M. (2015) · Histochemistry and Cell Biology · doi:10.1007/s00418-015-1366-7 · Cited by 46 · see citing works
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Ganeshpurkar, A., Swetha, R., Kumar, D., Gangaram, G. P., Singh, R., Gutti, G., Jana, S., Kumar, D., Kumar, A., & Singh, S. K. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190304153353 · Cited by 30 · see citing works
Ou-Yang, M.-H., & Van Nostrand, W. E. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-134 · Cited by 30 · see citing works
- Authors
- Zlokovic, B. V.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2004-04-13
- Volume
- 89
- Issue
- 4
- Pages
- 807-811
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2068631553
- Cited by
- 336
- References
- 34
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 1 · 2021: 8 · 2020: 3 · 2019: 4 · 2018: 11 · 2017: 16 · 2016: 17 · 2015: 11 · 2014: 20 · 2013: 21 · 2012: 22
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ag016223-04)
- National Institute on Aging (AG16223)
- National Institute of Neurological Disorders and Stroke (NS34467)
- 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
- amyloid-beta, blood-brain barrier, Alzheimer's disease, cerebrospinal fluid, amyloid hypothesis
- MeSH terms
- Receptor for Advanced Glycation End Products, Alzheimer Disease, Amyloid, Animals, Blood-Brain Barrier, Brain, Humans, Receptors, Immunologic, Amyloid beta-Peptides, LDL-Receptor Related Proteins
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