Abstract
Background: Alzheimer's disease (AD) is accompanied by a neuroinflammation triggering chemoattractant signals towards peripheral blood mononuclear cells (PBMCs), which in turn could reduce amyloid plaques after transmigration through the blood brain barrier (BBB). But the chemotactic environment remains unclear.
Objective: To analyze five chemokines known to be involved in AD in three different cellular models to better understand the cellular and molecular interactions in the BBB.
Method: Chemokines (CCL-2, 4 and 5, CXCL10 and CX3CL1) were measured in isolated cells, a BBB model without PBMCs (H4 and hCMEC/D3 cells, a neuroglioma and human endothelial cells, respectively) and in a complete BBB model with PBMCs from AD patients at a moderate stage. In one set of experiments, H4 cells were treated with Aβ42.
Results: CCL2 and CCL5 significantly increased in hCMEC/D3 and H4 cells in the complete BBB model. In turn, the rate of CCL2 increased in PBMCs whereas for CCL5, it decreased. CXCL10 increased in all cellular actors in the complete BBB model, compared to isolated cells. For CCL4, PBMCs induced a robust increase in H4 and hCMEC/D3. In turn, the level of CCL4 decreased in PBMCs. Furthermore, PBMCs triggered a significant increase in CX3CL1 in hCMEC/D3. Surprisingly, no effect of Aβ42 was observed in the complete BBB model.
Conclusion: These findings highlight the interest of a BBB model in order to explore chemokine production. For the first time, results showed that PBMCs from patients with AD can control the production of CCL4 and CXCL10 in a human BBB model.
Keywords: Chemokine, Alzheimer's disease, human BBB model, hCMEC/D3, PBMCs, Luminex®.
[2]
Cai Z, Hussain MD, Yan LJ. Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer’s disease. Int J Neurosci 124(5): 307-21. (2014).
[3]
Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging 21(3): 383-421. (2000).
[4]
Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 14(4): 388-405. (2015).
[5]
Heneka MT, Golenbock DT, Latz E. Innate immunity in Alzheimer’s disease. Nat Immunol 16(3): 229-36. (2015).
[6]
Guillot-Sestier MV, Doty KR, Town T. Innate immunity fights Alzheimer’s dsease. Trends Neurosci 38(11): 674-81. (2015).
[7]
Malm T, Koistinaho M, Muona A, Magga J, Koistinaho J. The role and therapeutic potential of monocytic cells in Alzheimer’s disease. Glia 58(8): 889-900. (2010).
[8]
Fisher Y, Nemirovsky A, Baron R, Monsonego A. T cells specifically targeted to amyloid plaques enhance plaque clearance in a mouse model of Alzheimer’s disease. PLoS One 5(5): e10830 (2010).
[9]
Simard AR, Rivest S. Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer’s disease. Mol Psychiatry 11(4): 327-35. (2006).
[10]
Hickman SE, El Khoury J. Mechanisms of mononuclear phagocyte recruitment in Alzheimer’s disease. CNS Neurol Disord Drug Targets 9(2): 168-73. (2010).
[11]
Lampron A, Gosselin D, Rivest S. Targeting the hematopoietic system for the treatment of Alzheimer’s disease. Brain Behav Immun 25(1): S71-9. (2011).
[12]
Rogers J, Luber-Narod J, Styren SD, Civin WH. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer’s disease. Neurobiol Aging 9(4): 339-49. (1988).
[13]
Di Marco LY, Venneri A, Farkas E, Evans PC, Marzo A, Frangi AF. Vascular dysfunction in the pathogenesis of Alzheimer’s disease: a review of endothelium-mediated mechanisms and ensuing vicious circles. Neurobiol Dis 82: 593-606. (2015).
[14]
Takeda S, Sato N, Morishita R. Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. Front Aging Neurosci 6: 171. (2014).
[16]
Alvarez JI, Katayama T, Prat A. Glial influence on the blood brain barrier. Glia 61(12): 1939-58. (2013).
[18]
Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 52(1): 145-76. (2000).
[19]
Williams JL, Holman DW, Klein RS. Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers. Front Cell Neurosci 8: 154. (2014).
[20]
Liu C, Cui G, Zhu M, Kang X, Guo H. Neuroinflammation in Alzheimer’s disease: chemokines produced by astrocytes and chemokine receptors. Int J Clin Exp Pathol 7(12): 8342-55. (2014).
[21]
Ruan L, Kong Y, Wang JM, Le Y. Chemoattractants and receptors in Alzheimer’s disease. Front Biosci (Schol Ed) 2: 504-14. (2010).
[22]
Lee YB, Nagai A, Kim SU. Cytokines, chemokines, and cytokine receptors in human microglia. J Neurosci Res 69(1): 94-103. (2002).
[23]
Zhang K, Tian L, Liu L, Feng Y, Dong YB, Li B, et al. CXCL1 contributes to beta-amyloid-induced transendothelial migration of monocytes in Alzheimer’s disease. PLoS One 8(8): e72744 (2013).
[24]
Bhaskar K, Konerth M, Kokiko-Cochran ON, Cardona A, Ransohoff RM, Lamb BT. Regulation of tau pathology by the microglial fractalkine receptor. Neuron 68(1): 19-31. (2010).
[25]
Krauthausen M, Kummer MP, Zimmermann J, Reyes-Irisarri E, Terwel D, Bulic B, et al. CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer’s disease model. J Clin Invest 125(1): 365-78. (2015).
[26]
Naert G, Rivest S. A deficiency in CCR2+ monocytes: the hidden side of Alzheimer’s disease. J Mol Cell Biol 5(5): 284-93. (2013).
[27]
Kiyota T, Gendelman HE, Weir RA, Higgins EE, Zhang G, Jain M. CCL2 affects beta-amyloidosis and progressive neurocognitive dysfunction in a mouse model of Alzheimer’s disease. Neurobiol Aging 34(4): 1060-8. (2013).
[28]
Fuhrmann M, Bittner T, Jung CK, Burgold S, Page RM, Mitteregger G, et al. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer’s disease. Nat Neurosci 13(4): 411-3. (2010).
[29]
Yamamoto M, Horiba M, Buescher JL, Huang D, Gendelman HE, Ransohoff RM, et al. Overexpression of monocyte chemotactic protein-1/CCL2 in beta-amyloid precursor protein transgenic mice show accelerated diffuse beta-amyloid deposition. Am J Pathol 166(5): 1475-85. (2005).
[30]
Liu YJ, Guo DW, Tian L, Shang DS, Zhao WD, Li B, et al. Peripheral T cells derived from Alzheimer’s disease patients overexpress CXCR2 contributing to its transendothelial migration, which is microglial TNF-alpha-dependent. Neurobiol Aging 31(2): 175-88. (2010).
[31]
Reale M, Iarlori C, Feliciani C, Gambi D. Peripheral chemokine receptors, their ligands, cytokines and Alzheimer’s disease. J Alzheimers Dis 14(2): 147-59. (2008).
[32]
Duan RS, Yang X, Chen ZG, Lu MO, Morris C, Winblad B, et al. Decreased fractalkine and increased IP-10 expression in aged brain of APP(swe) transgenic mice. Neurochem Res 33(6): 1085-9. (2008).
[33]
Xia MQ, Bacskai BJ, Knowles RB, Qin SX, Hyman BT. Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes: in vitro ERK1/2 activation and role in Alzheimer’s disease. J Neuroimmunol 108(1-2): 227-35. (2000).
[34]
Xia MQ, Qin SX, Wu LJ, Mackay CR, Hyman BT. Immunohistochemical study of the beta-chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer’s disease brains. Am J Pathol 153(1): 31-7. (1998).
[35]
Zhu M, Allard JS, Zhang Y, Perez E, Spangler EL, Becker KG, et al. Age-related brain expression and regulation of the chemokine CCL4/MIP-1beta in APP/PS1 double-transgenic mice. J Neuropathol Exp Neurol 73(4): 362-74. (2014).
[36]
Francois A, Julian A, Ragot S, Dugast E, Blanchard L, Brishoual S, et al. Inflammatory stress on autophagy in peripheral blood mononuclear cells from patients with Alzheimer’s disease during 24 months of follow-up. PLoS One 10(9): e0138326 (2015).
[37]
Julian A, Dugast E, Ragot S, Krolak-Salmon P, Berrut G, Dantoine T, et al. There is no correlation between peripheral inflammation and cognitive status at diagnosis in Alzheimer’s disease. Aging Clin Exp Res 27(5): 589-94. (2015).
[38]
Couturier J, Page G, Morel M, Gontier C, Claude J, Pontcharraud R, et al. Inhibition of double-stranded RNA-dependent protein kinase strongly decreases cytokine production and release in peripheral blood mononuclear cells from patients with Alzheimer’s disease. J Alzheimers Dis 21(4): 1217-31. (2010).
[39]
Iarlori C, Gambi D, Gambi F, Lucci I, Feliciani C, Salvatore M, et al. Expression and production of two selected beta-chemokines in peripheral blood mononuclear cells from patients with Alzheimer’s disease. Exp Gerontol 40(7): 605-11. (2005).
[40]
Magaki S, Mueller C, Dickson C, Kirsch W. Increased production of inflammatory cytokines in mild cognitive impairment. Exp Gerontol 42(3): 233-40. (2007).
[41]
Vedin I, Cederholm T, Freund-Levi Y, Basun H, Hjorth E, Irving GF, et al. Reduced prostaglandin F2 alpha release from blood mononuclear leukocytes after oral supplementation of omega3 fatty acids: the OmegAD study. J Lipid Res 51(5): 1179-85. (2010).
[42]
Poujol F, Monneret G, Pachot A, Textoris J, Venet F. Altered T lymphocyte proliferation upon lipopolysaccharide challenge ex vivo. PLoS One 10(12): e0144375 (2015).
[43]
Rocha NP, Teixeira AL, Coelho FM, Caramelli P, Guimaraes HC, Barbosa IG, et al. Peripheral blood mono-nuclear cells derived from Alzheimer’s disease patients show elevated baseline levels of secreted cytokines but resist stimulation with beta-amyloid peptide. Mol Cell Neurosci 49(1): 77-84. (2012).
[44]
Daniels BP, Cruz-Orengo L, Pasieka TJ, Couraud PO, Romero IA, Weksler B, et al. Immortalized human cerebral microvascular endothelial cells maintain the properties of primary cells in an in vitro model of immune migration across the blood brain barrier. J Neurosci Methods 212(1): 173-9. (2013).
[45]
Weksler BB, Subileau EA, Perriere N, Charneau P, Holloway K, Leveque M, et al. Blood-brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J 19(13): 1872-4. (2005).
[46]
Couturier J, Paccalin M, Morel M, Terro F, Milin S, Pontcharraud R, et al. Prevention of the beta-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures. Jof Neuroinflamm 8: 72. (2011).
[47]
Wilhelm I, Fazakas C, Krizbai IA. In vitro models of the blood-brain barrier. Acta Neurobiologiae Exp 71(1): 113-28. (2011).
[48]
Rezai-Zadeh K, Gate D, Gowing G, Town T. How to get from here to there: macrophage recruitment in Alzheimer’s disease. Curr Alzheimer Res 8(2): 156-63. (2011).
[49]
Streit WJ, Conde JR, Harrison JK. Chemokines and Alzheimer’s disease. Neurobiol Aging 22(6): 909-13. (2001).
[50]
Kelder W, McArthur JC, Nance-Sproson T, McClernon D, Griffin DE. Beta-chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia. Ann Neurol 44(5): 831-5. (1998).
[51]
Galimberti D, Schoonenboom N, Scarpini E, Scheltens P. Chemokines in serum and cerebrospinal fluid of Alzheimer’s disease patients. Ann Neurol 53(4): 547-8. (2003).
[52]
Stuart MJ, Baune BT. Chemokines and chemokine receptors in mood disorders, schizophrenia, and cognitive impairment: a systematic review of biomarker studies. Neurosci Biobehav Rev 42: 93-115. (2014).
[53]
Cardona SM, Garcia JA, Cardona AE. The fine balance of chemokines during disease: trafficking, inflammation, and homeostasis. Methods Mol Biol 1013: 1-16. (2013).
[54]
Khan TK, Alkon DL. Peripheral biomarkers of Alzheimer’s disease. J Alzheimers Dis 44(3): 729-44. (2015).
[55]
Song M, Jin J, Lim JE, Kou J, Pattanayak A, Rehman JA, et al. TLR4 mutation reduces microglial activation, increases Abeta deposits and exacerbates cognitive deficits in a mouse model of Alzheimer’s disease. J Neuroinflammation 8: 92. (2011).
[56]
Smits HA, Rijsmus A, van Loon JH, Wat JW, Verhoef J, Boven LA, et al. Amyloid-beta-induced chemokine production in primary human macrophages and astrocytes. J Neuroimmunol 127(1-2): 160-8. (2002).
[57]
Meda L, Baron P, Prat E, Scarpini E, Scarlato G, Cassatella MA, et al. Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with beta-amyloid [25-35]. J Neuroimmunol 93(1-2): 45-52. (1999).
[58]
Wang J, Li PT, Du H, Hou JC, Li WH, Pan YS, et al. Impact of paracrine signals from brain microvascular endothelial cells on microglial proliferation and migration. Brain research bulletin 86(1-2): 53-9. (2011).
[59]
Shukaliak JA, Dorovini-Zis K. Expression of the beta-chemokines RANTES and MIP-1 beta by human brain microvessel endothelial cells in primary culture. J Neuropathol Exp Neurol 59(5): 339-52. (2000).
[60]
Grzanna R, Phan P, Polotsky A, Lindmark L, Frondoza CG. Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes. J Altern Complement Med 10(6): 1009-13. (2004).
[61]
Rao S, Sengupta R, Choe EJ, Woerner BM, Jackson E, Sun T, et al. CXCL12 mediates trophic interactions between endothelial and tumor cells in glioblastoma. PLoS One 7(3): e33005 (2012).
[62]
Ramirez SH, Fan S, Zhang M, Papugani A, Reichenbach N, Dykstra H, et al. Inhibition of glycogen synthase kinase 3beta (GSK3beta) decreases inflammatory responses in brain endothelial cells. Am J Pathol 176(2): 881-92. (2010).
[63]
Correa JD, Starling D, Teixeira AL, Caramelli P, Silva TA. Chemokines in CSF of Alzheimer’s disease patients. Arquivos de Neuro-psiquiatria 69(3): 455-9. (2011).
[64]
Galimberti D, Schoonenboom N, Scheltens P, Fenoglio C, Venturelli E, Pijnenburg YA, et al. Intrathecal chemokine levels in Alzheimer disease and frontotemporal lobar degeneration. Neurology 66(1): 146-7. (2006).
[65]
Galimberti D, Venturelli E, Fenoglio C, Lovati C, Guidi I, Scalabrini D, et al. IP-10 serum levels are not increased in mild cognitive impairment and Alzheimer’s disease. Eur J Neurol 14(4): e3-4. (2007).
[66]
Vukic V, Callaghan D, Walker D, Lue LF, Liu QY, Couraud PO, et al. Expression of inflammatory genes induced by beta-amyloid peptides in human brain endothelial cells and in Alzheimer’s brain is mediated by the JNK-AP1 signaling pathway. Neurobiol Dis 34(1): 95-106. (2009).
[67]
Jehs T, Faber C, Juel HB, Nissen MH. Astrocytoma cells upregulate expression of pro-inflammatory cytokines after co-culture with activated peripheral blood mononuclear cells APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 119(8): 551-61 (2011).
[68]
Haskins M, Jones TE, Lu Q, Bareiss SK. Early alterations in blood and brain RANTES and MCP-1 expression and the effect of exercise frequency in the 3xTg-AD mouse model of Alzheimer’s disease. Neurosci Lett 610: 165-70. (2016).
[69]
Severini C, Passeri PP, Ciotti M, Florenzano F, Possenti R, Zona C, et al. Bindarit, inhibitor of CCL2 synthesis, protects neurons against amyloid-beta-induced toxicity. J Alzheimers Dis 38(2): 281-93. (2014).
[70]
Zhang R, Miller RG, Madison C, Jin X, Honrada R, Harris W, et al. Systemic immune system alterations in early stages of Alzheimer’s disease. J Neuroimmunol 256(1-2): 38-42. (2013).
[71]
Tripathy D, Thirumangalakudi L, Grammas P. RANTES upregulation in the Alzheimer’s disease brain: a possible neuroprotective role. Neurobiol Aging 31(1): 8-16. (2010).
[72]
Lee JK, Schuchman EH, Jin HK, Bae JS. Soluble CCL5 derived from bone marrow-derived mesenchymal stem cells and activated by amyloid beta ameliorates Alzheimer’s disease in mice by recruiting bone marrow-induced microglia immune responses. Stem Cells 30(7): 1544-55. (2012).
[73]
Bose S, Cho J. Role of chemokine CCL2 and its receptor CCR2 in neurodegenerative diseases. Arch Pharm Res 36(9): 1039-50. (2013).
[74]
Kiyota T, Yamamoto M, Schroder B, Jacobsen MT, Swan RJ, Lambert MP, et al. AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice. Mol Ther 17(5): 803-9. (2009).
[75]
Naert G, Rivest S. CC chemokine receptor 2 deficiency aggravates cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer’s disease. J Neurosci 31(16): 6208-20. (2011).
[76]
Naert G, Rivest S. Hematopoietic CC-chemokine receptor 2 (CCR2) competent cells are protective for the cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer’s disease. Mol Med 18: 297-313. (2012).
[77]
Mendes B, Marques C, Carvalho I, Costa P, Martins S, Ferreira D, et al. Influence of glioma cells on a new co-culture in vitro blood-brain barrier model for characterization and validation of permeability. Intern J Pharmaceutics 490(1-2): 94-101. (2015).
[78]
Salsman VS, Chow KK, Shaffer DR, Kadikoy H, Li XN, Gerken C, et al. Crosstalk between medulloblastoma cells and endothelium triggers a strong chemotactic signal recruiting T lymphocytes to the tumor microenvironment. PLoS One 6(5): e20267 (2011).
[79]
Desforges NM, Hebron ML, Algarzae NK, Lonskaya I, Moussa CE. Fractalkine mediates communication between pathogenic proteins and microglia: implications of anti-inflammatory treatments in different stages of neurodegenerative diseases. Int J Alzheimers Dis 2012: 345472 (2012).
[80]
Maciejewski-Lenoir D, Chen S, Feng L, Maki R, Bacon KB. Characterization of fractalkine in rat brain cells: migratory and activation signals for CX3CR-1-expressing microglia. J Immunol 163(3): 1628-35. (1999).
[81]
Hatori K, Nagai A, Heisel R, Ryu JK, Kim SU. Fractalkine and fractalkine receptors in human neurons and glial cells. J Neurosci Res 69(3): 418-26. (2002).
[82]
Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, et al. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91(4): 521-30. (1997).
[83]
Pan Y, Lloyd C, Zhou H, Dolich S, Deeds J, Gonzalo JA, et al. Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation. Nature 387(6633): 611-7. (1997).
[84]
Yoneda O, Imai T, Goda S, Inoue H, Yamauchi A, Okazaki T, et al. Fractalkine-mediated endothelial cell injury by NK cells. J Immunol 164(8): 4055-62. (2000).
[85]
Tong N, Perry SW, Zhang Q, James HJ, Guo H, Brooks A, et al. Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system. J Immunol 164(3): 1333-9. (2000).
[86]
Erreni M, Solinas G, Brescia P, Osti D, Zunino F, Colombo P, et al. Human glioblastoma tumours and neural cancer stem cells express the chemokine CX3CL1 and its receptor CX3CR1. Eur J Cancer 46(18): 3383-92. (2010).
[87]
Matsumiya T, Ota K, Imaizumi T, Yoshida H, Kimura H, Satoh K. Characterization of synergistic induction of CX3CL1/fractalkine by TNF-alpha and IFN-gamma in vascular endothelial cells: an essential role for TNF-alpha in post-transcriptional regulation of CX3CL1. J Immunol 184(8): 4205-14. (2010).
[88]
Imaizumi T, Yoshida H, Satoh K. Regulation of CX3CL1/fractalkine expression in endothelial cells. J Atheroscler Thromb 11(1): 15-21. (2004).
[89]
Fiala M, Zhang L, Gan X, Sherry B, Taub D, Graves MC, et al. Amyloid-beta induces chemokine secretion and monocyte migration across a human blood--brain barrier model. Mol Med 4(7): 480-9. (1998).
[90]
Hanzel CE, Pichet-Binette A, Pimentel LS, Iulita MF, Allard S, Ducatenzeiler A, et al. Neuronal driven pre-plaque inflammation in a transgenic rat model of Alzheimer’s disease. Neurobiol Aging 35(10): 2249-62. (2014).
[91]
Dworzak J, Renvoise B, Habchi J, Yates EV, Combadiere C, Knowles TP, et al. Neuronal Cx3cr1 deficiency protects against Amyloid beta-Induced neurotoxicity. PLoS One 10(6): e0127730 (2015).
[92]
Wu J, Bie B, Yang H, Xu JJ, Brown DL, Naguib M. Suppression of central chemokine fractalkine receptor signaling alleviates amyloid-induced memory deficiency. Neurobiol Aging 34(12): 2843-52. (2013).
[93]
Cho SH, Sun B, Zhou Y, Kauppinen TM, Halabisky B, Wes P, et al. CX3CR1 protein signaling modulates microglial activation and protects against plaque-independent cognitive deficits in a mouse model of Alzheimer disease. J Biol Chem 286(37): 32713-22. (2011).
[94]
Lee S, Xu G, Jay TR, Bhatta S, Kim KW, Jung S, et al. Opposing effects of membrane-anchored CX3CL1 on amyloid and tau pathologies via the p38 MAPK pathway. J Neurosci 34(37): 12538-46. (2014).
[95]
Lim JE, Kou J, Song M, Pattanayak A, Jin J, Lalonde R, et al. MyD88 deficiency ameliorates beta-amyloidosis in an animal model of Alzheimer’s disease. Am J Pathol 179(3): 1095-103. (2011).
[96]
Mizuno T. The biphasic role of microglia in Alzheimer’s disease. Int J Alzheimers Dis 2012737846 (2012).
[97]
Humpel C. Basolateral aggregated rat amyloidbeta(1-42) potentiates transmigration of primary rat monocytes through a rat blood-brain barrier. Curr Neurovasc Res 5(3): 185-92. (2008).
[98]
Giri R, Selvaraj S, Miller CA, Hofman F, Yan SD, Stern D, et al. Effect of endothelial cell polarity on beta-amyloid-induced migration of monocytes across normal and AD endothelium. Am J Physiol Cell Physiol 283(3): C895-904. (2002).
[99]
Strobel S, Grunblatt E, Riederer P, Heinsen H, Arzberger T, Al-Sarraj S, et al. Changes in the expression of genes related to neuroinflammation over the course of sporadic Alzheimer’s disease progression: CX3CL1, TREM2, and PPARgamma. J Neural Transm (Vienna) 122(7): 1069-76. (2015).
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