Toll-Like Receptors in Alzheimer's Disease

  • Gary E. LandrethEmail author
  • Erin G. Reed-Geaghan
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 336)


Alzheimer’s disease (AD) is characterized by the formation of insoluble deposits of β-amyloid (Aβ) within the parenchyma of the brain. These deposits are associated with a robust microglia-mediated inflammatory response. Recent work has demonstrated that Toll-like receptors (TLRs) participate in this inflammatory response. This chapter reviews the mechanisms whereby TLRs contribute to the induction of a microglial inflammatory response to promote AD pathogenesis. Specifically, the involvement of CD14 and the TLRs in microglial activation is delineated. The TLR-mediated microglial response has beneficial roles in stimulating phagocytosis as well as detrimental roles in the Aβ-stimulated release of neurotoxic products.


Microglial Activation Amyloid Precursor Protein Innate Immune Receptor Murine Microglia Proinflammatory Gene Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.




Alzheimer’s disease


Amyloid precursor protein




Formyl peptide receptor-like 1






IL-1 receptor-associated kinase


Interferon regulatory factor


Mitogen-activated protein kinase


Major histocompatibility complex II


Murine formyl peptide receptor 2


Myeloid differentiation primary response gene 88


Nonsteroidal anti-inflammatory drugs


Pattern recognition receptors


Pathogen-associated molecular patterns


Receptor-interacting protein 1


TAK1-binding proteins


TGF-β-activated kinase


TRAF family member-associated NF-κB activator binding kinase 1


Transforming growth factor-β


T-helper 2


Toll/IL-1 receptor


TIR-containing adaptor protein/MyD88 adaptor-like


Tumor necrosis factor α


Toll-like receptors


TNF-associated factor


TIR-domain-containing adaptor molecule/TRIF-related adaptor molecule 2


1 TIR-containing adaptor inducing IFN-β/TIR-domain containing adaptor molecule 1



This work was supported by the NIA (AG16047), the Blanchette Hooker Rockefeller Foundation, and the American Health Assistance Foundation. Erin Reed-Geaghan is supported by a predoctoral Ruth L. Kirschstein National Research Service Award (F31NS057867) from the NINDS.


  1. Adhikari A, Xu M, Chen Z (2007) Ubiquitin-mediated activation of TAK1 and IKK. Oncogene 26:3214–3226PubMedCrossRefGoogle Scholar
  2. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole G, Cooper N, Eikelenboom P, Emmerling M, Fiebich B, Finch C, Frautschy S, Griffin W, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie I, McGeer P, O’Banion K, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel F, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421PubMedCrossRefGoogle Scholar
  3. Arbour N, Lorenz E, Schutte B, Zabner J, Kline J, Jones M, Frees K, Watt J, Schwartz D (2000) TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 25:187–191PubMedCrossRefGoogle Scholar
  4. Bamberger ME, Harris ME, McDonald DR, Husemann J, Landreth GE (2003) A cell surface receptor complex for fibrillar beta-amyloid mediates microglial activation. J Neurosci 23:2665–2674PubMedGoogle Scholar
  5. Bate C, Kempster S, Williams A (2006) Prostaglandin D2 mediates neuronal damage by amyloid-beta or prions which activate microglial cells. Neuropharmacology 50:229–237PubMedCrossRefGoogle Scholar
  6. Bate C, Veerhuis R, Eikelenboom P, Williams A (2004) Microglia kill amyloid-b1–42 damaged neurons by a CD14-dependent process. NeuroReport 15:1427–1430PubMedCrossRefGoogle Scholar
  7. Blander J, Medzhitov R (2004) Regulation of phagosome maturation by signals from toll-like receptors. Science 304:1014–1018PubMedCrossRefGoogle Scholar
  8. Blasko I, Grubeck-Loebenstein B (2003) Role of the immune system in the pathogenesis, prevention and treatment of Alzheimer’s disease. Drugs Aging 20:101–113PubMedCrossRefGoogle Scholar
  9. Bolmont T, Haiss F, Eicke D, Radde R, Mathis C, Klunk W, Kohsaka S, Jucker M, Calhoun M (2008) Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J Neurosci 28:4283–4292PubMedCrossRefGoogle Scholar
  10. Bornemann K, Wiederhold K, Pauli C, Ermini F, Stalder M, Schnell L, Sommer B, Jucker M, Staufenbiel M (2001) Abeta-induced inflammatory processes in microglial cells of APP23 transgenic mice. Am J Pathol 158:63–73PubMedCrossRefGoogle Scholar
  11. Chan W, Kohsaka S, Rezaie P (2007) The origin and cell lineage of microglia: new concepts. Brain Res Rev 53:344–354PubMedCrossRefGoogle Scholar
  12. Chen F, Bhatia D, Chang Q, Castranova V (2006a) Finding NEMO by K63-linked polyubiquitin chain. Cell Death Differ 13:1835–1838CrossRefGoogle Scholar
  13. Chen K, Iribarren P, Hu J, Chen J, Gong W, Cho E, Lockett S, Dunlop N, Wang J (2006b) Activation of Toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid beta peptide. J Biol Chem 281:3651–3659CrossRefGoogle Scholar
  14. Combs C, Karlo J, Kao S, Landreth G (2001) Beta-amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci 21:1179–1188PubMedGoogle Scholar
  15. Crouch P, Harding S, White A, Camakaris J, Bush A, Masters C (2008) Mechanisms of Ab mediated neurodegeneration in Alzheimer’s disease. Int J Biochem Cell Biol 40:181–198PubMedCrossRefGoogle Scholar
  16. Cui Y, Le Y, Yazawa H, Gong W, Wang J (2002) Potential role for the formyl peptide receptor-like 1 (FPRL1) in inflammatory aspects of Alzheimer’s disease. J Leukoc Biol 72:628–635PubMedGoogle Scholar
  17. Cusson-Hermance N, Khurana S, Lee T, Fitzgerald K, Kelliher M (2005) Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation. J Biol Chem 280:36560–36566PubMedCrossRefGoogle Scholar
  18. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752–758PubMedCrossRefGoogle Scholar
  19. Dziedzic T (2006) Systemic inflammatory markers and risk of dementia. Am J Alzheimers Dis Other Demen 21:258–262PubMedCrossRefGoogle Scholar
  20. El Benna J, Han J, Park J, Schmid E, Ulevitch R, Babior B (1996) Activation of p38 in stimulated human neutrophils: phosphorylation of the oxidase component p47phox by p38 and ERK but not by JNK. Arch Biochem Biophys 334:395–400PubMedCrossRefGoogle Scholar
  21. Fassbender K, Walter S, Kuhl S, Landmann R, Ishii K, Bertsch T, Stalder A, Muehlhauser F, Liu Y, Ulmer A, Rivest S, Lentschat A, Gulbins E, Jucker M, Stafenbiel M, Brechtel K, Walter J, Multhaup G, Penke B, Adachi Y, Hartmann T, Beyreuther K (2004) The LPS receptor (CD14) links innate immunity with Alzheimer’s disease. FASEB J 18:203–205PubMedGoogle Scholar
  22. Fiala M, Liu P, Espinosa-Jeffery A, Rosenthal M, Bernard G, Ringman J, Sayre M, Zhang L, Zaghi J, Dejbakhsh S, Chiang B, Hui J, Mahanian M, Baghaee A, Hong P, Cashman J (2007) Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer’s disease patients are improved by bisdemethoxycurcumin. Proc Natl Acad Sci USA 104:12849–12854PubMedCrossRefGoogle Scholar
  23. Findeis M (2007) The role of amyloid b peptide 42 in Alzheimer’s disease. Pharmacol Ther 116:266–286PubMedCrossRefGoogle Scholar
  24. Fitzgerald K, McWhirter S, Faia K, Rowe D, Latz E, Golenbock D, Coyle A, Liao S, Maniatis T (2003) IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 4:491–496PubMedCrossRefGoogle Scholar
  25. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann NY Acad Sci 908:244–254PubMedCrossRefGoogle Scholar
  26. Fratiglioni L, Winblad B, von Strauss E (2007) Prevention of Alzheimer’s disease and dementia. Major findings from the Kungsholmen Project. Physiol Behav 92:98–104PubMedCrossRefGoogle Scholar
  27. Goerdt S, Orfanos CE (1999) Other functions, other genes: alternative activation of antigen-presenting cells. Immunity 10:137–142PubMedCrossRefGoogle Scholar
  28. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–35PubMedCrossRefGoogle Scholar
  29. Gorelick P (2004) Risk factors for vascular dementia and Alzheimer’s disease. Stroke 35:2620–2622PubMedCrossRefGoogle Scholar
  30. Haga S, Akai K, Ishii T (1989) Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody. Acta Neuropathol (Berl) 77:569–575CrossRefGoogle Scholar
  31. Han J, Ulevitch R (2005) Limiting inflammatory responses during activation of innate immunity. Nat Immunol 6:1198–1205PubMedCrossRefGoogle Scholar
  32. Hanisch U, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394PubMedCrossRefGoogle Scholar
  33. Hickman SE, Allison EK, El Khoury J (2008) Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J Neurosci 28:8354–8360PubMedCrossRefGoogle Scholar
  34. in’t Veld B, Ruitenberg A, Launer J (2000) Duration of nonsteroidal anti-inflammatory drug use and risk of Alzheimer’s disease. The Rotterdam study. Neurobiol Aging 21:S204CrossRefGoogle Scholar
  35. Iribarren P, Chen K, Hu J, Gong W, Cho E, Lockett S, Uranchimeg B, Wang J (2005a) CpG-containing oligodeoxynucleotide promotes microglial cell uptake of amyloid beta 1–42 peptide by up-regulating the expression of the G-protein-coupled receptor mFPR2. FASEB J 19:2032–2034Google Scholar
  36. Iribarren P, Zhou Y, Hu J, Le Y, Wang J (2005b) The role of formyl peptide receptor like 1 (FPRL1/MFPR2) in mononuclear phagocyte responses in Alzheimer’s disease. Immunol Res 31:165–176CrossRefGoogle Scholar
  37. Jana M, Palencia CA, Pahan K (2008) Fibrillar amyloid-beta peptides activate microglia via TLR2: implications for Alzheimer’s disease. J Immunol 181:7254–7262PubMedGoogle Scholar
  38. Jankowsky J, Fadale D, Anderson J, Xu G, Gonzales V, Jenkins N, Copeland N, Lee M, Younkin L, Wagner S, Younkin S, Borchelt D (2004) Mutant presenilins specifically elevate levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Human Mol Genet 13:159–170CrossRefGoogle Scholar
  39. Jiang Z, Mak T, Sen G, Li X (2004) Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta. Proc Natl Acad Sci USA 101:3533–3538PubMedCrossRefGoogle Scholar
  40. Jin JJ, Kim HD, Maxwell JA, Li L, Fukuchi K (2008) Toll-like receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer’s disease. J Neuroinflammation 5:23Google Scholar
  41. Kawai T, Akira S (2007) Signaling to NF-kB by Toll-like receptors. Trends Mol Med 13:460–469PubMedCrossRefGoogle Scholar
  42. Kielian T (2006) Toll-like receptors in central nervous system glial inflammation and homeostasis. J Neurosci Res 83:711–730PubMedCrossRefGoogle Scholar
  43. Koenigsknecht J, Landreth G (2004) Microglial phagocytosis of fibrillar beta-amyloid through a beta1 integrin-dependent mechanism. J Neurosci 24:9838–9846PubMedCrossRefGoogle Scholar
  44. Koenigsknecht-Talboo J, Landreth GE (2005) Microglial phagocytosis induced by fibrillar beta-amyloid and IgGs are differentially regulated by pro-inflammatory cytokines. J Neurosci 25:8240–8249PubMedCrossRefGoogle Scholar
  45. Letiembre M, Hao W, Liu Y, Walter S, Mihaljevic I, Rivest S, Hartmann T, Fassbender K (2007) Innate immune receptor expression in normal brain aging. Neuroscience 146:248–254PubMedCrossRefGoogle Scholar
  46. Letiembre M, Liu Y, Walter S, Hao W, Pfander T, Wrede A, Schulz-Schaeffer W, Fassbender K (2009) Screening of innate immune receptors in neurodegenerative diseases: a similar pattern. Neurobiol Aging 30:759–768PubMedCrossRefGoogle Scholar
  47. Liu Y, Walter S, Stagi M, Cherny D, Letiembre M, Schulz-Schaeffer W, Heine H, Penke B, Neumann H, Fassbender K (2005) LPS receptor (CD14): a receptor for phagocytosis of Alzheimer’s amyloid peptide. Brain 128:1778–1789PubMedCrossRefGoogle Scholar
  48. Lotz M, Ebert S, Esselmann H, Iliev A, Prinz M, Wiazewicz N, Wiltfang J, Gerber J, Nau R (2005) Amyloid beta peptide 1–40 enhances action of Toll like receptor-2 and -4 agonists but antagonizes Toll-like receptor-9-induced inflammation in primary mouse microglial cell cultures. J Neurochem 94:289–298PubMedCrossRefGoogle Scholar
  49. Luber-Narod J, Rogers J (1988) Immune system associated antigens expressed by cells of the human central nervous system. Neurosci Lett 94:17–22PubMedCrossRefGoogle Scholar
  50. Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549–555PubMedCrossRefGoogle Scholar
  51. McDonald DR, Bamberger ME, Combs CK, Landreth GE (1998) b-Amyloid fibrils activate parallel mitogen-activated protein kinase pathways in microglia and THP-1 monocytes. J Neurosci 18:4451–4460PubMedGoogle Scholar
  52. McGeer P, Akiyama H, Itagaki S, McGeer E (1989) Immune system response in Alzheimer’s disease. Can J Neurol Sci 16:516–527PubMedGoogle Scholar
  53. McGeer P, Schulzer M, McGeer E (1996) Arthritis and antiiinflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiological studies. Neurology 47:425–432PubMedGoogle Scholar
  54. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145PubMedCrossRefGoogle Scholar
  55. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, Tschopp J (2004) RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol 5:503–507PubMedCrossRefGoogle Scholar
  56. Minoretti P, Gazzaruso C, Vito C, Emanuele E, Bianchi M, Coen E, Reino M, Geroldi D (2006) Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility of late-onset Alzheimer’s disease. Neurosci Lett 391:147–149PubMedCrossRefGoogle Scholar
  57. Neumann H, Wekerle H (1998) Neuronal control of the immune response in the central nervous system: linking brain immunity to neurodegeneration. J Neuropathol Exp Neurol 57:1–9PubMedCrossRefGoogle Scholar
  58. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318PubMedCrossRefGoogle Scholar
  59. Nomura F, Kawai T, Nakanishi K, Akira S (2000) NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation. Genes Cells 5:191–202PubMedCrossRefGoogle Scholar
  60. Patel N, Paris D, Mathura V, Quadros A, Crawford F, Mullan M (2005) Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer’s disease. J Neuroinflammation 2:9Google Scholar
  61. Poltorak A, He X, Smirnova I, Liu M, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciari-Castagnoli P, Layton B, Beutler B (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in TLR4 gene. Science 282:2085–2088PubMedCrossRefGoogle Scholar
  62. Pomerantz J, Baltimore D (1999) NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. EMBO J 18:6694–6704PubMedCrossRefGoogle Scholar
  63. Ransohoff R (2007) Microgliosis: the questions shape the answers. Nat Neurosci 10:1507–1509PubMedCrossRefGoogle Scholar
  64. Reed-Geaghan E, Landreth G (2007) CD14 and its associated toll like receptors mediate microglial activation by fAb. In: Society for Neuroscience (ed) 2007 Neuroscience Meeting Planner, vol 688. Society for Neuroscience, San DiegoGoogle Scholar
  65. Rich JB, Rasmusson DX, Folstein MF, Carson KA, Kawas C, Brandt J (1995) Nonsteroidal anti-inflammatory drugs in Alzheimer’s disease. Neurology 45:51–55PubMedGoogle Scholar
  66. Richard KL, Filali M, Prefontaine P, Rivest S (2008) Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid beta 1–42 and delay the cognitive decline in a mouse model of Alzheimer’s disease. J Neurosci 28:5784–5793PubMedCrossRefGoogle Scholar
  67. Rodriguez-Rodriguez E, Sanchez-Juan P, Mateo I, Infante J, Sanchez-Quintana C, Garcia-Gorostiaga I, Berciano J, Combarros O (2008) Interaction between CD14 and LXRbeta genes modulates Alzheimer’s disease risk. J Neurol Sci 264:97–99PubMedCrossRefGoogle Scholar
  68. Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, Zalinski J, Cofield M, Mansukhani L, Willson P, et al. (1993) Clinical trial of indomethacin in Alzheimer’s disease. Neurology 43:1609–1611PubMedGoogle Scholar
  69. Rogers J, Luber-Narod J, Styren S, Civin W (1988) Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer’s disease. Neurobiol Aging 9:339–349PubMedCrossRefGoogle Scholar
  70. Sanjo H, Takeda K, Tsujimura T, Ninomiya-Tsuji J, Matsumoto K, Akira S (2003) TAB2 is essential for prevention of apoptosis in fetal liver but not for interleukin-1 signaling. Mol Cell Biol 23:1231–1238PubMedCrossRefGoogle Scholar
  71. Sato S, Sugiyama M, Yamamoto M, Watanabe Y, Kawai T, Takeda K, Akira S (2003) Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. J Immunol 171:4303–4310Google Scholar
  72. Selkoe D (2000) Toward a comprehensive theory for Alzheimer’s disease. Hypothesis: Alzheimer’s disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein. Ann NY Acad Sci 924:17–25PubMedCrossRefGoogle Scholar
  73. Seong S, Matzinger P (2004) Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses. Nat Rev 4:469–478CrossRefGoogle Scholar
  74. Sharma S, tenOever B, Grandvaux N, Zhou G, Lin R, Hiscott J (2003) Triggering the interferon antiviral response through an IKK-related pathway. Science 300:1148–1151PubMedCrossRefGoogle Scholar
  75. Shim J, Xiao C, Paschal A, Bailey S, Rao P, Hayden M, Lee K, Bussey C, Steckel M, Tanaka N, Yamada G, Akira S, Matsumoto K, Ghosh S (2005) TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev 19:2668–2681PubMedCrossRefGoogle Scholar
  76. Simard A, Rivest S (2004) Bone marrow stem cells have the ability to populate the entire central nervous system into fully differentiated parenchymal microglia. FASEB J 18:998–1000PubMedGoogle Scholar
  77. Stalder M, Deller T, Staufenbiel M, Jucker M (2001) 3D-reconstruction of microglia and amyloid in APP23 transgenic mice: no evidence of intracellular amyloid. Neurobiol Aging 22:427–434PubMedCrossRefGoogle Scholar
  78. Stewart W, Kawas C, Corrada M, Metter E (1997) Rish of Alzheimer’s disease and duration of NSAID use. Neurology 4:626–632Google Scholar
  79. Styren S, Civin W, Rogers J (1990) Molecular, cellular, and pathologic characterization of HLA-DR immunoreactivity in normal elderly and Alzheimer’s disease brain. Exp Neurol 110:93–104PubMedCrossRefGoogle Scholar
  80. Tahara K, Kim H, Jin J, Maxwell J, Li L, Fukuchi K (2006) Role of toll-like receptor signalling in Abeta uptake and clearance. Brain 129:3006–3019PubMedCrossRefGoogle Scholar
  81. Tiffany H, Lavigne M, Cui Y, Wang J, Leto T, Gao J, Murphy M (2001) Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide receptor 2, a G protein-coupled receptor expressed in phagocytes and brain. J Biol Chem 276:645–652CrossRefGoogle Scholar
  82. Tsan M, Gao B (2007) Pathogen-associated molecular pattern contamination as putative endogenous ligands of Toll-like receptors. J Endotoxin Res 13:6–14PubMedCrossRefGoogle Scholar
  83. Udan M, Ajit D, Crouse N, Nichols M (2008) Toll-like receptors 2 and 4 mediate Ab(1–42) activation of the innate immune response in a human monocytic cell line. J Neurochem 104:524–533PubMedGoogle Scholar
  84. Walter S, Letiembre M, Liu Y, Heine H, Penke B, Hao W, Bode B, Manietta N, Walter J, Schulz-Schaeffer W, Fassbender K (2007) Role of the Toll-like receptor 4 in neuro-inflammation in Alzheimer’s disease. Cell Physiol Biochem 20:947–956PubMedCrossRefGoogle Scholar
  85. Wang C, Deng L, Hong M, Akkaraju G, Inoue J, Chen Z (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346–351PubMedCrossRefGoogle Scholar
  86. Wilkinson B, Koenigsknecht-Talboo J, Grommes C, Lee CY, Landreth G (2006) Fibrillar beta-amyloid-stimulated intracellular signaling cascades require Vav for induction of respiratory burst and phagocytosis in monocytes and microglia. J Biol Chem 281:20842–20850PubMedCrossRefGoogle Scholar
  87. Yamamoto M, Sato S, Mori K, Hoshino K, Takeuchi O, Takeda K, Akira S (2002) A novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 169:6668–6672PubMedGoogle Scholar
  88. Yazawa H, Yu Z, Takeda X, Le Y, Gong W, Ferrans V, Oppenheim J, Li C, Wang J (2001) Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages. FASEB J 15:2454–2462PubMedCrossRefGoogle Scholar
  89. Ying G, Iribarren P, Zhou Y, Gong W, Zhang N, Yu Z, Le Y, Cui Y, Wang J (2004) Humanin, a newly identified neuroprotective factor, uses the G protein coupled formylpeptide receptor-like-1 as a functional receptor. J Immunol 172:7078–7085PubMedGoogle Scholar
  90. Younkin S (1998) The role of A beta 42 in Alzheimer’s disease. J Physiol Paris 92:289–292PubMedCrossRefGoogle Scholar
  91. Zelcer N, Khanlou N, Clare R, Jiang Q, Reed-Geaghan E, Landreth G, Vinters H, Tontonoz P (2007) Attenuation of neuroinflammation and Alzheimer’s disease pathology by liver x receptors. Proc Natl Acad Sci USA 104:10601–10606PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Alzheimer Research Laboratory, Department of NeurosciencesCase Western Reserve UniversityClevelandUSA

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