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Licensed Unlicensed Requires Authentication Published by De Gruyter December 10, 2018

The role of neurovascular unit damage in the occurrence and development of Alzheimer’s disease

Xin Liu, DeRen Hou, FangBo Lin, Jing Luo, JingWen Xie, Yan Wang and Yi Tian

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease with progressive cognitive impairment. It is the most common type of senile dementia, accounting for 65%–70% of senile dementia [Alzheimer’s Association (2016). 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 12, 459–509]. At present, the pathogenesis of AD is still unclear. It is considered that β-amyloid deposition, abnormal phosphorylation of tau protein, and neurofibrillary tangles are the basic pathological changes of AD. However, the role of neurovascular unit damage in the pathogenesis of AD has been attracting more and more attention in recent years. The composition of neurovascular unit and the role of neurovascular unit damage in the occurrence and development of AD were reviewed in this paper.

Acknowledgments

The work was supported by the Focus on Research and Development Plan of Science & Technology Department of Hunan Province of China (2016JC2052) and by the New Xiangya Talent Project of the Third Xiangya Hospital of Central South University (20150305).

References

Alzheimer’s Association. (2016). 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 12, 459–509.10.1016/j.jalz.2016.03.001Search in Google Scholar PubMed

Bading, J.R., Yamada, S., Mackic, J.B., Kirkman, L., Miller, C., Calero, M., Ghiso, J., Frangione, B., and Zlokovic, B.V. (2002). Brain clearance of Alzheimer’s amyloid-β40 in the squirrel monkey: a SPECT study in a primate model of cerebral amyloid angiopathy. Drug Target 10, 359–368.10.1080/10611860290031831Search in Google Scholar PubMed

Barros, L.F., San Martín, A., Ruminot, I., Sandoval, P.Y., Fernández-Moncada, I., Baeza-Lehnert, F., Arce-Molina, R., Contreras-Baeza, Y., Cortés-Molina, F., Galaz, A., et al. (2017). Near-critical GLUT1 and neurodegeneration. J. Neurosci. Res. 95, 2267–2274.10.1002/jnr.23998Search in Google Scholar PubMed

Bell, R.D. and Zlokovic, B.V. (2009). Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease. Acta Neuropathol. 118, 103–113.10.1007/s00401-009-0522-3Search in Google Scholar PubMed PubMed Central

Blusztajn, J.K. and Berse, B. (2000). The cholinergic neuronal phenotype in Alzheimer’s disease. Metab. Brain Dis. 15, 45–64.10.1007/BF02680013Search in Google Scholar PubMed

Cai, Z., Liu, N., Wang, C., Qin, B., Zhou, Y., Xiao, M., Chang, L., Yan, L.J., and Zhao, B. (2016). Role of RAGE in Alzheimer’s disease. Cell Mol. Neurobiol. 36, 483–495.10.1007/s10571-015-0233-3Search in Google Scholar PubMed

Chen, W., Chan, Y., Wan, W., Li, Y., and Zhang, C. (2018). Aβ induces cell damage via RAGE-dependent endoplasmic reticulum stress in bEnd.3 cells. Exp. Cell Res. 362, 83–89.10.1016/j.yexcr.2017.11.005Search in Google Scholar PubMed

Deane, R., Du, Y.S., Submamaryan, R.K., LaRue, B., Jovanovic, S., Hogg, E., Welch, D., Manness, L., Lin, C., Yu, J., et al. (2003). RAGE mediates amyloid-beta peptide transport across the blood–brain barrier and accumulation in brain. Nat. Med. 9, 907–913.10.1038/nm890Search in Google Scholar PubMed

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). LRP/amyloid beta-peptide interaction mediates differential brain efflux of Aβ isoforms. Neuron 43, 333–344.10.1016/j.neuron.2004.07.017Search in Google Scholar PubMed

Deane, R., Singh, I., Sagare, A.P., Bell, R.D., Ross, N.T., LaRue, B., Love, R., Perry, S., Paquette, N., Deane, R.J., et al. (2012). A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. J. Clin. Invest. 122, 1377–1392.10.1172/JCI58642Search in Google Scholar PubMed PubMed Central

Donahue, J.E., Flaherty, S.L., Johanson, C.E., Duncan, J.A., Silverberg, G.D., Miller, M.C., Tavares, R., Yang, W., Wu, Q., Sabo, E., et al. (2006). RAGE, LRP-1, and amyloid-βeta protein in Alzheimer‘s disease. Acta Neuropathol. 112, 405–415.10.1007/s00401-006-0115-3Search in Google Scholar PubMed

Duits, F.H., Hernandez, G.M., Montaner, J., Goos, J.D., Montañola, A., Wattjes, M.P., Barkhof, F., Scheltens, P., Teunissen, C.E., and van der Flier, W.M. (2015). Matrix metalloproteinases in Alzheimer’s disease and concurrent cerebral microbleeds. J. Alzheimers Dis. 48, 711–720.10.3233/JAD-143186Search in Google Scholar PubMed

Gąsiorowski, K., Brokos, B., Echeverria, V., Barreto, G.E., and Leszek, J. (2018). RAGE-TLR crosstalk sustains chronic inflammation in neurodegeneration. Mol. Neurobiol. 55, 1463–1476.10.1007/s12035-017-0419-4Search in Google Scholar PubMed

Halliday, M.R., Rege, S.V., Ma, Q., Zhao, Z., Miller, C.A., Winkler, E.A., and Zloković, B.V. (2016). Accelerated pericyte degeneration and blood–brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer. J. Cereb. Blood Flow Metab. 36, 216–227.10.1038/jcbfm.2015.44Search in Google Scholar PubMed PubMed Central

Hernández-Guillamon, M., Delgado, P., Ortega, L., Pares, M., Rosell, A., García-Bonill, L., Fernández-Cadenas, I., Borrell-Pagès, M., Boada, M., and Montaner, J. (2009). Neuronal TIMP-1 release accompanies astrocytic MMP-9 secretion and enhances astrocyte proliferation induced by β-amyloid 25–35 fragment. J. Neurosci. Res. 87, 2115–2125.10.1002/jnr.22034Search in Google Scholar PubMed

Honjo, Y., Ayaki, T., Tomiyama, T., Horibe, T., Ito, H., Mori, H., Takahashi, R., and Kawakami, K. (2015). Increased GADD34 in oligodendrocytes in Alzheimer’s disease. Neurosci. Lett. 602, 50–55.10.1016/j.neulet.2015.06.052Search in Google Scholar PubMed

Honjo, Y., Ayaki, T., Tomiyama, T., Horibe, T., Ito, H., Mori, H., Takahashi, R., and Kawakami, K. (2017). Decreased levels of PDI and P5 in oligodendrocytes in Alzheimer’s disease. Neuropathology 37, 495–501.10.1111/neup.12395Search in Google Scholar PubMed

Ikonomovic, M.D., Abrahamson, E.E., Isanski, B.A., Wuu, J., Mufson, E.J., and DeKosky, S.T. (2007). Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease. Arch. Neurol. 4, 1312–1317.10.1001/archneur.64.9.1312Search in Google Scholar PubMed

Iturria-Medina, Y., Sotero, R.C., Toussaint, P.J., Mateos-Pérez, J.M., and Evans, A.C. (2016). Alzheimer’s Disease Neuroimaging Initiative. Nat. Commun. 7, 11934.10.1038/ncomms11934Search in Google Scholar PubMed PubMed Central

Jaeger, L.B., Dohgu, S., Hwang, M.C., Farr, S.A., Murphy, M.P., Fleegal-DeMotta, M.A., Lynch, J.L., Robinson, S.M., Niehoff, M.L., Johnson, S.N., et al. (2009). Testing the neurovascular hypothesis of Alzheimer‘s disease: LRP-1 antisense reduces blood–brain barrier clearance, increases brain levels of amyloid-β protein, and impairs cognition. J. Alzheimer’s Dis. 17, 553–570.10.3233/JAD-2009-1074Search in Google Scholar PubMed PubMed Central

Kang, D.E., Pietrzik, C.U., Baum, L., Chevallier, N., Merriam, D.E., Kounnas, M.Z., Wagner, S.L., Troncoso, J.C., Kawas, C.H., Katzman, R., et al. (2000). Modulation of amyloid beta-protein clearance and Alzheimer’s disease susceptibility by the LDL receptor-related protein pathway. Clin. Invest. 106, 1159–1166.10.1172/JCI11013Search in Google Scholar

Kannan, M., Manivel, P., Geetha, K., Muthukumaran, J., Rao, H.S., and Krishna, R. (2012). Synthesis and in silico evaluation of 1N-methyl-1S-methyl-2-nitroethylene (NMSM) derivatives against Alzheimer disease: to understand their interacting mechanism with acetylcholinesterase. J. Chem. Biol. 5, 151–166.10.1007/s12154-012-0084-zSearch in Google Scholar PubMed

Kisler, K., Nelson, A.R., Montagne, A., and Zloković, B.V. (2017). Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat. Rev. Neurosci. 18, 419–434.10.1038/nrn.2017.48Search in Google Scholar PubMed

Kumar, V., Sulaj, A., Fleming, T., and Nawroth, P.P. (2018). Purification and characterization of the soluble form of the receptor for advanced glycation end-products (sRAGE): a novel fast, economical and convenient method. Exp. Clin. Endocrinol. Diabet. 126, 141–147.10.1055/s-0043-110478Search in Google Scholar

Leijenaar, J.F., van Maurik, I.S., Kuijer, J.P.A., vanderFlier, W.M., Scheltens, P., Barkhof, F., and Prins, N.D. (2017). Lower cerebral blood flow in subjects with Alzheimer’s dementia, mild cognitive impairment, and subjective cognitive decline using two-dimensional phase-contrast magnetic resonance imaging. Alzheimers Dement(Amst.) 9, 76–83.10.1016/j.dadm.2017.10.001Search in Google Scholar PubMed

Martel, C.L., Mackic, J.B., McComb, J.G., Ghiso, J., and Zloković, B.V. (1996). Blood–brain barrier uptake of the 40 and 42 amino acid sequences of circulating Alzheimer’s amyloid β in guinea pigs. Neurosci. Lett. 206, 157–160.10.1016/S0304-3940(96)12462-9Search in Google Scholar PubMed

Martin, E. and Delarasse, C. (2018). Complex role of chemokine mediators in animal models of Alzheimer’s Disease. Biomed. J. 41, 34–40.10.1016/j.bj.2018.01.002Search in Google Scholar PubMed PubMed Central

Mawuenyega, K.G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J.C., Yarasheski, K.E., and Bateman, R.J. (2010). Decreased clearance of CNS β-amyloid in Alzheimer’s disease. Science 330, 1774.10.1126/science.1197623Search in Google Scholar PubMed PubMed Central

Miller, M.C., Tavares, R., Johanson, C.E., Hovanesian, V., Donahue, J.E., Gonzalez, L., Silverberg, G.D., and Stopa, E.G. (2008). Hippocampal RAGE immunoreactivity in early and advanced Alzheimer’s disease. Brain Res. 1230, 273–280.10.1016/j.brainres.2008.06.124Search in Google Scholar PubMed PubMed Central

Mroczko, B., Groblewska, M., Zboch, M., Kulczyńska, A., Koper, O.M., Szmitkowski, M., Kornhuber, J., and Lewczuk, P. (2014). Concentrations of matrix metalloproteinases and their tissue inhibitors in the cerebrospinal fluid of patients with Alzheimer’s disease. J. Alzheimers Dis. 40, 351–357.10.3233/JAD-131634Search in Google Scholar PubMed

Mustaly-Kalimi, S., Littlefield, A.M., and Stutzmann, G.E. (2018). Calcium signaling deficits in glia and autophagic pathways contributing to neurodegenerative disease. Antioxid. Redox Signal. 29, 1158–1175.10.1089/ars.2017.7266Search in Google Scholar PubMed

Nelson, A.R., Sweeney, M.D., Sagare, A.P., and Zloković, B.V. (2016). Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer’s disease. Biochim. Biophys. Acta 1862, 887–900.10.1016/j.bbadis.2015.12.016Search in Google Scholar PubMed PubMed Central

Nelson, A.R., Sagare, A.P., and Zloković, B.V. (2017). Role of clusterin in the brain vascular clearance of amyloid-β. Proc. Natl. Acad. Sci. USA 114, 8681–8682.10.1073/pnas.1711357114Search in Google Scholar PubMed PubMed Central

Norden, D.M. and Godbout, J.P. (2018). Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathol. Appl. Neurobiol. 39, 19–34.10.1111/j.1365-2990.2012.01306.xSearch in Google Scholar PubMed PubMed Central

Poddar, J., Pradhan, M., Ganguly, G., and Chakrabarti, S. (2018). Biochemical deficits and cognitive decline in brain aging: intervention by dietary supplements. J. Chem. Neuroanat. doi: 10.1016/j.jchemneu.2018.04.002. [Epub ahead of print].10.1016/j.jchemneu.2018.04.002Search in Google Scholar PubMed

Ramanathan, A., Nelson, A.R., Sagare, A.P., and Zloković, B.V. (2015). Impaired vascular-mediated clearance of brain amyloid β in Alzheimer’s disease: the role, regulation and restoration of LRP1. Front. Aging Neurosci. 7, 136.10.3389/fnagi.2015.00136Search in Google Scholar PubMed PubMed Central

Ranjit, G., Yamin, S., Monique, S., Shi, D.Y., Ann, M.S., David, S., Kwang-Sik, K., Berislav, Z., and Vijay, K.K. (2000). β-Amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1. Am. J. Physiol. Cell Physiol 279, C1772–C1781.10.1152/ajpcell.2000.279.6.C1772Search in Google Scholar PubMed

Sagare, A., Deane, R., Bell, P.D., Johnson, B., Hamm, K., Pendu, R., Marky, A., Lenting, P.J., Wu, Z., Zarcone, T., et al. (2007). Clearance of amyloid-β by circulating lipoprotein receptors. Clearance of amyloid-beta by circulating lipoprotors. Nat. Med. 13, 1029–1031.10.1038/nm1635Search in Google Scholar PubMed PubMed Central

Sagare, A.P., Bel, R.D., Zhao, Z., Ma, Q., Winkler, E.A., Ramanathan, A., and Zloković, B.V. (2013a). Pericyte loss influences Alzheimer-like neurodegeneration in mice. Nat. Commun. 4, 2932.10.1038/ncomms3932Search in Google Scholar PubMed PubMed Central

Sagare, A.P., Bell, R.D., and Zloković, B.V. (2013b). Neurovascular defects and faulty amyloid-β vascular clearance in Alzheimer’s disease. J. Alzheimers Dis. 33, S87–S100.10.3233/JAD-2012-129037Search in Google Scholar PubMed PubMed Central

Sanderson, R.D., Bandari, S.K., and Vlodavsky, I. (2017). Proteases and glycosidases on the surface of exosomes: newly discovered mechanisms for extracellular remodeling. Matrix Biol. doi: 10.1016/j.matbio.2017.10.007. [Epub ahead of print].10.1016/j.matbio.2017.10.007Search in Google Scholar PubMed PubMed Central

Sá Santos, S., Santos, S.M., Pinto, A.R., Ramu, V.G., Heras, M., Bardaji, E., Tavares, I., and Castanho, M.A. (2016). Amidated and ibuprofen-conjugated kyotorphin promote neuronal rescue and memory recovery in cerebral hypoperfusion dementia model. Front. Aging Neurosci. 8, 1.10.3389/fnagi.2016.00001Search in Google Scholar PubMed PubMed Central

Sengillo, J.D., Winkler, E.A., Walker, C.T., Sullivan, J.S., Johnson, M., and Zloković, B.V. (2013). Deficiency in mural vascular cells coincides with blood–brain barrier disruption in Alzheimer’s dissease. Brain Pathol. 23, 303–310.10.1111/bpa.12004Search in Google Scholar PubMed PubMed Central

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). Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor related protein-1 at the blood–brain barrier. Clin. Invest. 106, 1489–1499.10.1172/JCI10498Search in Google Scholar PubMed PubMed Central

Simpson, I.A., Carruthers, A., and Vannucci, S.J. (2007). Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J. Cereb. Blood. Flow. Metab. 27, 1766–1791.10.1038/sj.jcbfm.9600521Search in Google Scholar PubMed PubMed Central

Sweeney, M.D., Sagare, A.P., and Zloković, B.V. (2015). Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer’s disease. J. Cereb. Blood Flow Metab. 35, 1055–1068.10.1038/jcbfm.2015.76Search in Google Scholar PubMed PubMed Central

Sweeney, M.D., Ayyadurai, S., and Zloković, B.V. (2016). Pericytes of the neurovascular unit: key functions and signaling pathways. Nat. Neurosci. 19, 771–783.10.1038/nn.4288Search in Google Scholar PubMed PubMed Central

Sweeney, M.D., Sagare, A.P., and Zloković, B.V. (2018). Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat. Rev. Neurol. 14, 133–150.10.1038/nrneurol.2017.188Search in Google Scholar PubMed PubMed Central

Szablewski, L. (2017). Glucose transporters in brain: in health and in Alzheimer’s disease. J. Alzheimers Dis. 55, 1307–1320.10.3233/JAD-160841Search in Google Scholar PubMed

Tamaki, C., Ohtsuki, S., Iwatsubo, T., Hashimoto, T., Yamada, K., Yabuki, C., and Terasaki, T. (2006). Major involvement of low-density lipoprotein receptor-related protein 1 in the clearance of plasma free amyloid β-peptide by the liver. Pharm. Res. 23, 1407–1416.10.1007/s11095-006-0208-7Search in Google Scholar PubMed

Tarasoff-Conway, J.M., Carare, R.O., Osorio, R.S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zloković, B.V., et al. (2015). Clearance systems in the brain–implications for Alzheimer disease. Nat. Rev. Neurol. 11, 457–470.10.1038/nrneurol.2015.119Search in Google Scholar PubMed PubMed Central

Tomobe, K., Okuma, Y., and Nomura, Y. (2007). Impairment of CREB phosphorylation in the hippocampal CA1 region of the senescence-accelerated mouse (SAM) P8. Brain Res. 1141, 214–217.10.1016/j.brainres.2006.08.026Search in Google Scholar PubMed

Uchida, Y., Tachikawa, M., Obuchi, W., Hoshi, Y., Tomioka, Y., Ohtsuki, S., and Terasaki, T. (2013). A study protocol for quantitative targeted absolute proteomics (QTAP) by LC-MS/MS: application for inter-strain differences in protein expression levels of transporters, receptors, claudin-5, and marker proteins at the blood–brain barrier in ddY, FVB, and C57BL/6J mice. Fluids Barriers CNS 10, 21.10.1186/2045-8118-10-21Search in Google Scholar PubMed PubMed Central

Winkler, E.A., Sagare, A.P., and Zloković, B.V. (2014). The pericyte: a forgotten cell type with important implications for Alzheimer’s disease? Brain Pathol. 24, 371–386.10.1111/bpa.12152Search in Google Scholar PubMed PubMed Central

Winkler, E.A., Nishida, Y., Sagare, A.P., Rege, S.V., Bell, R.D., Perlmutter, D., Sengillo, J.D., Hillman, S., Kong, P., Nelson, A.R., et al. (2015). GLUT1 reductions exacerbate Alzheimer’s disease vasculo-neuronal dysfunction and degeneration. Nat. Neurosci. 18, 521–530.10.1038/nn.3966Search in Google Scholar PubMed PubMed Central

Wu, Y., Ma, Y., Liu, Z., Geng, Q., Chen, Z., and Zhang, Y. (2017). Alterations of myelin morphology and oligodendrocyte development in early stage of Alzheimer’s disease mouse model. Neurosci. Lett. 642, 102–106.10.1016/j.neulet.2017.02.007Search in Google Scholar PubMed

Xin, S.H., Tan, L., Cao, X., Yu, J.T., and Tan, L. (2018). Clearance of amyloid beta and tau in Alzheimer’s Disease: from mechanisms to therapy. Neurotox. Res. 34, 733–748.10.1007/s12640-018-9895-1Search in Google Scholar PubMed

Zhang, G.R., Cheng, X.R., Zhou, W.X., and Zhang, Y.X. (2009). Age-related expression of calcium/calmodulin-dependent protein kinase II A in the hippocampus and cerebral cortex of senescence accelerated mouse prone/8 mice is modulated by anti-Alzheimer’s disease drugs. Neuroscience 159, 308–315.10.1016/j.neuroscience.2008.06.068Search in Google Scholar PubMed

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). Central role for PICALM in amyloid-β blood–brain barrier transcytosis and clearance. Nat. Neurosci. 18, 978–987.10.1038/nn.4025Search in Google Scholar PubMed PubMed Central

Zhao, H., Wang, Q., Cheng, X., Li, X., Li, N., Liu, T., Li, J., Yang, Q., Dong, R., Zhang, Y., et al. (2018). Inhibitive effect of resveratrol on the inflammation in cultured astrocytes and microglia induced by Aβ. Neuroscience 379, 390–404.10.1016/j.neuroscience.2018.03.047Search in Google Scholar PubMed

Zloković, B.V. (1995). Cerebrovascular permeability to peptides: manipulations of transport systems at the blood–brain barrier. Pharm. Res. 12, 1395–1406.10.1023/A:1016254514167Search in Google Scholar PubMed

Zloković, B.V. (2011). Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat. Rev. Neurosci. 12, 723–738.10.1038/nrn3114Search in Google Scholar PubMed

Zloković, B.V. and Apuzzo, M.L. (1997). Cellular and molecular neurosurgery: pathways from concept to reality–part I: target disorders and concept approaches to gene therapy of the central nervous system. Neurosurgery. 40, 789–803.10.1097/00006123-199704000-00027Search in Google Scholar PubMed

Zloković, B.V., Begley, D.J., and Chain-Eliash, D.G. (1985a). Blood–brain barrier permeability to leucine-enkephalin, D-alanine2-D-leucine5-enkephalin and their N-terminal amino acid (tyrosine). Brain Res. 336, 125–132.10.1016/0006-8993(85)90423-8Search in Google Scholar

Zloković, B.V., Segal, M.B., Begley, D.J., Davson, H., and Rakić, L. (1985b). Permeability of the blood–cerebrospinal fluid and blood–brain barriers to thyrotropin-releasing hormone. Brain Res. 358, 191–199.10.1016/0006-8993(85)90963-1Search in Google Scholar

Zloković, B.V., Lipovac, M.N., Begley, D.J., Davson, H., and Rakić, L. (1987). Transport of leucine-enkephalin across the blood–brain barrier in the perfused guinea pig brain. J. Neurochem. 49, 310–315.10.1111/j.1471-4159.1987.tb03431.xSearch in Google Scholar PubMed

Zloković, B.V., Hyman, S., McComb, J.G., Lipovac, M.N., Tang, G., and Davson, H. (1990). Kinetics of arginine-vasopressin uptake at the blood–brain barrier. Biochim. Biophys. Acta 1025, 191–198.10.1016/0005-2736(90)90097-8Search in Google Scholar PubMed

Zloković, B.V., Deane, R., Sagare, A.P., Bell, R.D., and Winkler, E.A. (2010). Low-density lipoprotein receptor-related protein-1: a serial clearance homeostatic mechanism controlling Alzheimer’s amyloid β-peptide elimination from the brain. J. Neurochem. 115, 1077–1089.10.1111/j.1471-4159.2010.07002.xSearch in Google Scholar PubMed PubMed Central

Received: 2018-06-06
Accepted: 2018-08-30
Published Online: 2018-12-10
Published in Print: 2019-07-26

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