APOE-modulated Aβ-induced neuroinflammation in Alzheimer's disease: Current landscape, novel data, and future perspective

Journal of Neurochemistry

Volumn 133, Issue 4, 2015, Pages 465-488

  Tai, Leon M ^a   Ghura, Shivesh ^a   Koster, Kevin P ^a   Liakaite, Vaiva ^a   Maienschein Cline, Mark ^a   Kanabar, Pinal ^a   Collins, Nicole ^a   Ben Aissa, Manel ^a   Lei, Arden Zhengdeng ^a   Bahroos, Neil ^a   Green, Stefan J ^a   Hendrickson, Bill ^a   Van Eldik, Linda J ^b   LaDu, Mary Jo ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Alzheimer's disease; amyloid ; apolipoprotein E; interleukin 4 receptor; neuroinflammation; toll like receptor 4

Indexed keywords

AMYLOID BETA PROTEIN; APOLIPOPROTEIN E; APOLIPOPROTEIN E2; APOLIPOPROTEIN E3; APOLIPOPROTEIN E4; AUTACOID; CELECOXIB; CHF 5074; ETANERCEPT; FLURBIPROFEN; INTERLEUKIN 4 RECEPTOR; NAPROXEN; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN SYNTHASE; SYNAPTOPHYSIN; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; CELL ACTIVATION; DISEASE COURSE; DRUG TARGETING; ENZYME INHIBITION; GENETIC RISK; GENOTYPE; GLIA CELL; HUMAN; MEDICAL RESEARCH; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SYSTEMATIC REVIEW; ANIMAL; COMPLICATION; DRUG EFFECTS; GENETICS; GLIA; INFLAMMATION; METABOLISM; PHYSIOLOGY;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; APOLIPOPROTEINS E; HUMANS; INFLAMMATION; NEUROGLIA; SIGNAL TRANSDUCTION;

EID: 84927594690     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/jnc.13072     Document Type: Review

References (236)

1. ADAPT-FS-Research-Group (2014) Follow-up evaluation of cognitive function in the randomized Alzheimer's Disease Anti-inflammatory Prevention Trial and its Follow-up Study. Alzheimers Dement. doi: 10.1016/j.jalz.2014.03.009.
2. ADAPT-Research-Group (2013) Results of a follow-up study to the randomized Alzheimer's disease Anti-inflammatory Prevention Trial (ADAPT). Alzheimers Dement. 9, 714-723.
3. Aguzzi A., Barres B. A., and, Bennett M. L., (2013) Microglia: scapegoat, saboteur, or something else? Science 339, 156-161.
4. Akiyama H., Barger S., Barnum S., et al,. (2000) Inflammation and Alzheimer's disease. Neurobiol. Aging 21, 383-421.
5. Azevedo O. G., Bolick D. T., Roche J. K., Pinkerton R. F., Lima A. A., Vitek M. P., Warren C. A., Oria R. B., and, Guerrant R. L., (2014) Apolipoprotein E plays a key role against cryptosporidial infection in transgenic undernourished mice. PLoS ONE 9, e89562.
6. Bachstetter A. D., and, Van Eldik L. J., (2010) The p38 MAP kinase family as regulators of proinflammatory cytokine production in degenerative diseases of the CNS. Aging Dis. 1, 199-211.
7. Bachstetter A. D., Watterson D. M., and, Van Eldik L. J., (2014) Target engagement analysis and link to pharmacodynamic endpoint for a novel class of CNS-penetrant and efficacious p38alpha MAPK inhibitors. J. Neuroimmune Pharmacol. 9, 454-460.
8. Banks W. A., and, Robinson S. M., (2010) Minimal penetration of lipopolysaccharide across the murine blood-brain barrier. Brain Behav. Immun. 24, 102-109.
9. Begum A. N., Cunha C., Sidhu H., Alkam T., Scolnick J., Rosario E. R., and, Ethell D. W., (2014) Women with the Alzheimer's risk marker ApoE4 lose Aβ-specific CD4(+) T cells 10-20 years before men. Transl. Psychiatry 4, e414.
10. Belinson H., and, Michaelson D. M., (2009) ApoE4-dependent Aβ-mediated neurodegeneration is associated with inflammatory activation in the hippocampus but not the septum. J. Neural. Transm. 116, 1427-1434.
11. Bell R. D., Winkler E. A., Singh I., et al,. (2012) Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485, 512-516.
12. Benoit M., Desnues B., and, Mege J. L., (2008) Macrophage polarization in bacterial infections. J. Immunol. 181, 3733-3739.
13. Bettoni I., Comelli F., Rossini C., Granucci F., Giagnoni G., Peri F., and, Costa B., (2008) Glial TLR4 receptor as new target to treat neuropathic pain: efficacy of a new receptor antagonist in a model of peripheral nerve injury in mice. Glia 56, 1312-1319.
14. Boda E., Pini A., Hoxha E., Parolisi R., and, Tempia F., (2009) Selection of reference genes for quantitative real-time RT-PCR studies in mouse brain. J. Mol. Neurosci. 37, 238-253.
15. Boehm-Cagan A., and, Michaelson D. M., (2014) Reversal of apoE4-driven brain pathology and behavioral deficits by bexarotene. J. Neurosci. 34, 7293-7301.
16. de Bont N., Netea M. G., Demacker P. N., Verschueren I., Kullberg B. J., van Dijk K. W., van der Meer J. W., and, Stalenhoef A. F., (1999) Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection. J. Lipid Res. 40, 680-685.
17. Bowman C. C., Rasley A., Tranguch S. L., and, Marriott I., (2003) Cultured astrocytes express toll-like receptors for bacterial products. Glia 43, 281-291.
18. Bradshaw E. M., Chibnik L. B., Keenan B. T., et al,. (2013) CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology. Nat. Neurosci. 16, 848-850.
19. Breitner J. C., Baker L. D., Montine T. J., et al,. (2011) Extended results of the Alzheimer's disease anti-inflammatory prevention trial. Alzheimers Dement. 7, 402-411.
20. Britschgi M., Takeda-Uchimura Y., Rockenstein E., Johns H., Masliah E., and, Wyss-Coray T., (2012) Deficiency of terminal complement pathway inhibitor promotes neuronal tau pathology and degeneration in mice. J. Neuroinflammation 9, 220.
21. Brouwers N., Van Cauwenberghe C., Engelborghs S., et al,. (2012) Alzheimer risk associated with a copy number variation in the complement receptor 1 increasing C3b/C4b binding sites. Mol. Psychiatry 17, 223-233.
22. Brown C. M., Wright E., Colton C. A., Sullivan P. M., Laskowitz D. T., and, Vitek M. P., (2002) Apolipoprotein E isoform mediated regulation of nitric oxide release. Free Radic. Biol. Med. 32, 1071-1075.
23. Bsibsi M., Ravid R., Gveric D., and, van Noort J. M., (2002) Broad expression of Toll-like receptors in the human central nervous system. J. Neuropathol. Exp. Neurol. 61, 1013-1021.
24. Bu G., (2009) Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy. Nat. Rev. Neurosci. 10, 333-344.
25. Buchanan M. M., Hutchinson M., Watkins L. R., and, Yin H., (2010) Toll-like receptor 4 in CNS pathologies. J. Neurochem. 114, 13-27.
26. Butchart J., and, Holmes C., (2012) Systemic and central immunity in Alzheimer's disease: therapeutic implications. CNS Neurosci. Ther. 18, 64-76.
27. Butovsky O., Jedrychowski M. P., Moore C. S., et al,. (2014) Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 17, 131-143.
28. Cameron B., and, Landreth G. E., (2010) Inflammation, microglia, and Alzheimer's disease. Neurobiol. Dis. 37, 503-509.
29. Carpentier P. A., Begolka W. S., Olson J. K., Elhofy A., Karpus W. J., and, Miller S. D., (2005) Differential activation of astrocytes by innate and adaptive immune stimuli. Glia 49, 360-374.
30. Cash J. G., Kuhel D. G., Basford J. E., Jaeschke A., Chatterjee T. K., Weintraub N. L., and, Hui D. Y., (2012) Apolipoprotein E4 impairs macrophage efferocytosis and potentiates apoptosis by accelerating endoplasmic reticulum stress. J. Biol. Chem. 287, 27876-27884.
31. Chakrabarty P., Tianbai L., Herring A., Ceballos-Diaz C., Das P., and, Golde T. E., (2012) Hippocampal expression of murine IL-4 results in exacerbation of amyloid deposition. Mol. Neurodegener. 7, 36.
32. Chen Y., Durakoglugil M. S., Xian X., and, Herz J., (2010) ApoE4 reduces glutamate receptor function and synaptic plasticity by selectively impairing ApoE receptor recycling. Proc. Natl Acad. Sci. USA 107, 12011-12016.
33. Cherry J. D., Olschowka J. A., and, O'Banion M. K., (2014) Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J. Neuroinflammation 11, 98.
34. Chhor V., Le Charpentier T., Lebon S., et al,. (2013) Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro. Brain Behav. Immun. 32, 70-85.
35. Chouraki V., and, Seshadri S., (2014) Genetics of Alzheimer's disease. Adv. Genet. 87, 245-294.
36. Colton C. A., Xu Q., Burke J. R., Bae S. Y., Wakefield J. K., Nair A., Strittmatter W. J., and, Vitek M. P., (2004) Disrupted spermine homeostasis: a novel mechanism in polyglutamine-mediated aggregation and cell death. J. Neurosci. 24, 7118-7127.
37. Colton C. A., Mott R. T., Sharpe H., Xu Q., Van Nostrand W. E., and, Vitek M. P., (2006) Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. J. Neuroinflammation 3, 27.
38. Cook N. L., Vink R., Donkin J. J., and, van den Heuvel C., (2009) Validation of reference genes for normalization of real-time quantitative RT-PCR data in traumatic brain injury. J. Neurosci. Res. 87, 34-41.
39. Crehan H., Holton P., Wray S., Pocock J., Guerreiro R., and, Hardy J., (2012) Complement receptor 1 (CR1) and Alzheimer's disease. Immunobiology 217, 244-250.
40. Cruchaga C., Kauwe J. S., Nowotny P., et al,. (2012) Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease. Hum. Mol. Genet. 21, 4558-4571.
41. Cudaback E., Yang Y., Montine T. J., and, Keene C. D., (2015) APOE genotype-dependent modulation of astrocyte chemokine CCL3 production. Glia 63, 51-65.
42. Dergunov A. D., Smirnova E. A., Merched A., Visvikis S., Siest G., Yakushkin V. V., and, Tsibulsky V., (2000) Conformation of apolipoprotein E both in free and in lipid-bound form may determine the avidity of triglyceride-rich lipoproteins to the LDL receptor: structural and kinetic study. Biochim. Biophys. Acta 1484, 14-28.
43. DiCarlo G., Wilcock D., Henderson D., Gordon M., and, Morgan D., (2001) Intrahippocampal LPS injections reduce Aβ load in APP+PS1 transgenic mice. Neurobiol. Aging 22, 1007-1012.
44. Dorey E., Chang N., Liu Q. Y., Yang Z., and, Zhang W., (2014) Apolipoprotein E, amyloid-beta, and neuroinflammation in Alzheimer's disease. Neurosci. Bull. 30, 317-330.
45. Drye L. T., and, Zandi P. P., (2012) Role of APOE and age at enrollment in the Alzheimer's disease anti-inflammatory prevention trial (ADAPT). Dement. Geriatr. Cogn. Dis. Extra 2, 304-311.
46. Edison P., Archer H. A., Gerhard A., et al,. (2008) Microglia, amyloid, and cognition in Alzheimer's disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol. Dis. 32, 412-419.
47. Eikelenboom P., and, van Gool W. A., (2004) Neuroinflammatory perspectives on the two faces of Alzheimer's disease. J. Neural. Transm. 111, 281-294.
48. Ennaciri J., and, Girard D., (2009) IL-4R(alpha), a new member that associates with Syk kinase: implication in IL-4-induced human neutrophil functions. J. Immunol. 183, 5261-5269.
49. Falsig J., Latta M., and, Leist M., (2004) Defined inflammatory states in astrocyte cultures: correlation with susceptibility towards CD95-driven apoptosis. J. Neurochem. 88, 181-193.
50. Farlow M. R., Lahiri D. K., Poirier J., Davignon J., Schneider L., and, Hui S. L., (1998) Treatment outcome of tacrine therapy depends on apolipoprotein genotype and gender of the subjects with Alzheimer's disease. Neurology 50, 669-677.
51. Fenn A. M., Henry C. J., Huang Y., Dugan A., and, Godbout J. P., (2012) Lipopolysaccharide-induced interleukin (IL)-4 receptor-alpha expression and corresponding sensitivity to the M2 promoting effects of IL-4 are impaired in microglia of aged mice. Brain Behav. Immun. 26, 766-777.
52. Ferretti M. T., and, Cuello A. C., (2011) Does a pro-inflammatory process precede Alzheimer's disease and mild cognitive impairment? Curr. Alzheimer Res. 8, 164-174.
53. Fisher C. A., and, Ryan R. O., (1999) Lipid binding-induced conformational changes in the N-terminal domain of human apolipoprotein E. J. Lipid Res. 40, 93-99.
54. Ford J. W., and, McVicar D. W., (2009) TREM and TREM-like receptors in inflammation and disease. Curr. Opin. Immunol. 21, 38-46.
55. Fuller J. P., Stavenhagen J. B., and, Teeling J. L., (2014) New roles for Fc receptors in neurodegeneration-the impact on immunotherapy for Alzheimer's disease. Front. Neurosci. 8, 235.
56. Gadani S. P., Cronk J. C., Norris G. T., and, Kipnis J., (2012) IL-4 in the brain: a cytokine to remember. J. Immunol. 189, 4213-4219.
57. Gale S. C., Gao L., Mikacenic C., et al,. (2014) APOepsilon4 is associated with enhanced in vivo innate immune responses in human subjects. J. Allergy Clin. Immunol. 134, 127-134.
58. Gordon S., (2003) Alternative activation of macrophages. Nat. Rev. Immunol. 3, 23-35.
59. Gorelick P. B., (2010) Role of inflammation in cognitive impairment: results of observational epidemiological studies and clinical trials. Ann. N. Y. Acad. Sci. 1207, 155-162.
60. Green A. E., Gray J. R., Deyoung C. G., Mhyre T. R., Padilla R., Dibattista A. M., and, William Rebeck G., (2014) A combined effect of two Alzheimer's risk genes on medial temporal activity during executive attention in young adults. Neuropsychologia 56, 1-8.
61. Griffin W. S., and, Mrak R. E., (2002) Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer's disease. J. Leukoc. Biol. 72, 233-238.
62. Griffin W. S. T., Stanley L. C., Ling C., White L., MacLeod V., Perrot L. J., White C. L., and, Araoz C., (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc. Natl Acad. Sci. USA 86, 7611-7615.
63. Gubern C., Hurtado O., Rodriguez R., Morales J. R., Romera V. G., Moro M. A., Lizasoain I., Serena J., and, Mallolas J., (2009) Validation of housekeeping genes for quantitative real-time PCR in in-vivo and in-vitro models of cerebral ischaemia. BMC Mol. Biol. 10, 57.
64. Guerreiro R., Wojtas A., Bras J., et al,. (2013) TREM2 variants in Alzheimer's disease. N. Engl. J. Med. 368, 117-127.
65. Guo L., LaDu M. J., and, Van Eldik L. J., (2004) A dual role for apolipoprotein e in neuroinflammation: anti- and pro-inflammatory activity. J. Mol. Neurosci. 23, 205-212.
66. Haass C., and, Selkoe D. J., (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat. Rev. Mol. Cell Biol. 8, 101-112.
67. Hanamsagar R., Hanke M. L., and, Kielian T., (2012) Toll-like receptor (TLR) and inflammasome actions in the central nervous system. Trends Immunol. 33, 333-342.
68. Hardy J., (2006) Alzheimer's disease: the amyloid cascade hypothesis: an update and reappraisal. J. Alzheimers Dis. 9, 151-153.
69. Hardy J., Bogdanovic N., Winblad B., Portelius E., Andreasen N., Cedazo-Minguez A., and, Zetterberg H., (2014) Pathways to Alzheimer's disease. J. Intern. Med. 275, 296-303.
70. Hashioka S., Monji A., Ueda T., Kanba S., and, Nakanishi H., (2005) Amyloid-beta fibril formation is not necessarily required for microglial activation by the peptides. Neurochem. Int. 47, 369-376.
71. Hauser P. S., Narayanaswami V., and, Ryan R. O., (2011) Apolipoprotein E: from lipid transport to neurobiology. Prog. Lipid Res. 50, 62-74.
72. Hayden E. Y., and, Teplow D. B., (2013) Amyloid beta-protein oligomers and Alzheimer's disease. Alzheimers Res. Ther. 5, 60.
73. Hennessy E. J., Parker A. E., and, O'Neill L. A., (2010) Targeting toll-like receptors: emerging therapeutics? Nat. Rev. Drug Discov. 9, 293-307.
74. Herber D. L., Roth L. M., Wilson D., Wilson N., Mason J. E., Morgan D., and, Gordon M. N., (2004) Time-dependent reduction in Aβ levels after intracranial LPS administration in APP transgenic mice. Exp. Neurol. 190, 245-253.
75. Herber D. L., Mercer M., Roth L. M., Symmonds K., Maloney J., Wilson N., Freeman M. J., Morgan D., and, Gordon M. N., (2007) Microglial activation is required for Aβ clearance after intracranial injection of lipopolysaccharide in APP transgenic mice. J. Neuroimmune Pharmacol. 2, 222-231.
76. Hickman S. E., and, El Khoury J., (2014) TREM2 and the neuroimmunology of Alzheimer's disease. Biochem. Pharmacol. 88, 495-498.
77. Hickman S. E., Allison E. K., and, El Khoury J., (2008) Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice. J. Neurosci. 28, 8354-8360.
78. Hickman S. E., Kingery N. D., Ohsumi T. K., Borowsky M. L., Wang L. C., Means T. K., and, El Khoury J., (2013) The microglial sensome revealed by direct RNA sequencing. Nat. Neurosci. 16, 1896-1905.
79. Hirsch-Reinshagen V., Zhou S., Burgess B. L., et al,. (2004) Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain. J. Biol. Chem. 279, 41197-41207.
80. Hollingworth P., Harold D., Sims R., et al,. (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nat. Genet. 43, 429-435.
81. Holtzman D. M., Herz J., and, Bu G., (2012) Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harb. Perspect Med. 2, a006312.
82. Hong S., Quintero-Monzon O., Ostaszewski B. L., Podlisny D. R., Cavanaugh W. T., Yang T., Holtzman D. M., Cirrito J. R., and, Selkoe D. J., (2011) Dynamic analysis of amyloid beta-protein in behaving mice reveals opposing changes in ISF versus parenchymal Aβ during age-related plaque formation. J. Neurosci. 31, 15861-15869.
83. Hu J., LaDu M. J., and, Van Eldik L. J., (1998) Apolipoprotein E attenuates beta-amyloid-induced astrocyte activation. J. Neurochem. 71, 1626-1634.
84. Hudry E., Dashkoff J., Roe A. D., et al,. (2013) Gene transfer of human apoe isoforms results in differential modulation of amyloid deposition and neurotoxicity in mouse brain. Sci. Transl. Med. 5, 212ra161.
85. Imbimbo B. P., Solfrizzi V., and, Panza F., (2010) Are NSAIDs useful to treat Alzheimer's disease or mild cognitive impairment? Front. Aging Neurosci. 2, doi: 10.3389/fnagi.2010.00019.
86. Jiang T., Yu J. T., Hu N., Tan M. S., Zhu X. C., and, Tan L., (2014) CD33 in Alzheimer's disease. Mol. Neurobiol. 49, 529-535.
87. Jin J. J., Kim H. D., Maxwell J. A., Li L., and, Fukuchi K., (2008) Toll-like receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer's disease. J. Neuroinflammation 5, 23.
88. Jin M., Shepardson N., Yang T., Chen G., Walsh D., and, Selkoe D. J., (2011) Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc. Natl Acad. Sci. USA 108, 5819-5824.
89. Jofre-Monseny L., Loboda A., Wagner A. E., Huebbe P., Boesch-Saadatmandi C., Jozkowicz A., Minihane A. M., Dulak J., and, Rimbach G., (2007) Effects of apoE genotype on macrophage inflammation and heme oxygenase-1 expression. Biochem. Biophys. Res. Commun. 357, 319-324.
90. Jonsson T., Stefansson H., Steinberg S., et al,. (2013) Variant of TREM2 associated with the risk of Alzheimer's disease. N. Engl. J. Med. 368, 107-116.
91. Karran E., and, Hardy J., (2014) Antiamyloid therapy for Alzheimer's disease-are we on the right road? N. Engl. J. Med. 370, 377-378.
92. Keene C. D., Cudaback E., Li X., Montine K. S., and, Montine T. J., (2011) Apolipoprotein E isoforms and regulation of the innate immune response in brain of patients with Alzheimer's disease. Curr. Opin. Neurobiol. 21, 920-928.
93. Kelly M. E., Clay M. A., Mistry M. J., Hsieh-Li H. M., and, Harmony J. A., (1994) Apolipoprotein E inhibition of proliferation of mitogen-activated T lymphocytes: production of interleukin 2 with reduced biological activity. Cell. Immunol. 159, 124-139.
94. Kessler Y., Helfer-Hungerbuehler A. K., Cattori V., et al,. (2009) Quantitative TaqMan real-time PCR assays for gene expression normalisation in feline tissues. BMC Mol. Biol. 10, 106.
95. Klein W. L., (2002) Aβ toxicity in Alzheimer's disease: globular oligomers (ADDLs) as new vaccine and drug targets. Neurochem. Int. 41, 345-352.
96. Krishnaswamy G., Kelley J., Yerra L., Smith J. K., and, Chi D. S., (1999) Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease. J. Interferon Cytokine Res. 19, 91-104.
97. Kunzler J., Youmans K. L., Yu C., Ladu M. J., and, Tai L., (2013) APOE modulates the effect of estrogen therapy on Aβ accumulation EFAD-Tg mice. Neurosci. Lett. 560, 131-136.
98. Kuo Y. M., Emmerling M. R., Vigo-Pelfrey C., Kasunic T. C., Kirkpatrick J. B., Murdoch G. H., Ball M. J., and, Roher A. E., (1996) Water-soluble Aβ (N-40, N-42) oligomers in normal and Alzheimer disease brains. J. Biol. Chem. 271, 4077-4081.
99. LaDu M. J., Reardon C., Van Eldik L., Fagan A. M., Bu G., Holtzman D., and, Getz G. S., (2000) Lipoproteins in the central nervous system. Ann. N. Y. Acad. Sci. 903, 167-175.
100. LaDu M. J., Shah J. A., Reardon C. A., Getz G. S., Bu G., Hu J., Guo L., and, Van Eldik L. J., (2001) Apolipoprotein E and apolipoprotein E receptors modulate A beta-induced glial neuroinflammatory responses. Neurochem. Int. 39, 427-434.
101. LaDu M. J., Stine W. B., Jr, Narita M., Getz G. S., Reardon C. A., and, Bu G., (2006) Self-assembly of HEK cell-secreted ApoE particles resembles ApoE enrichment of lipoproteins as a ligand for the LDL receptor-related protein. Biochemistry 45, 381-390.
102. Lambert J. C., Ibrahim-Verbaas C. A., Harold D., et al,. (2013) Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat. Genet. 45, 1452-1458.
103. Lambracht-Washington D., and, Rosenberg R. N., (2013) Anti-amyloid beta to tau-based immunization: developments in immu-notherapy for Alzheimer disease. Immunotargets Ther. 2013, 105-114.
104. Landreth G. E., (2009) Microglia in central nervous system diseases. J. Neuroimmune Pharmacol. 4, 369-370.
105. Landreth G. E., and, Reed-Geaghan E. G., (2009) Toll-like receptors in Alzheimer's disease. Curr. Top. Microbiol. Immunol. 336, 137-153.
106. Lazarov O., and, Marr R. A., (2013) Of mice and men: neurogenesis, cognition and Alzheimer's disease. Front. Aging Neurosci. 5, 43.
107. Lee J. W., Lee Y. K., Yuk D. Y., Choi D. Y., Ban S. B., Oh K. W., and, Hong J. T., (2008) Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J. Neuroinflammation 5, 37.
108. Lefterov I., Bookout A., Wang Z., Staufenbiel M., Mangelsdorf D., and, Koldamova R., (2007) Expression profiling in APP23 mouse brain: inhibition of Aβ amyloidosis and inflammation in response to LXR agonist treatment. Mol. Neurodegener. 2, 20.
109. Lehnardt S., (2010) Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia 58, 253-263.
110. Lehnardt S., Lachance C., Patrizi S., Lefebvre S., Follett P. L., Jensen F. E., Rosenberg P. A., Volpe J. J., and, Vartanian T., (2002) The toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J. Neurosci. 22, 2478-2486.
111. Lehnardt S., Massillon L., Follett P., Jensen F. E., Ratan R., Rosenberg P. A., Volpe J. J., and, Vartanian T., (2003) Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway. Proc. Natl Acad. Sci. USA 100, 8514-8519.
112. Leon C. G., Tory R., Jia J., Sivak O., and, Wasan K. M., (2008) Discovery and development of toll-like receptor 4 (TLR4) antagonists: a new paradigm for treating sepsis and other diseases. Pharm. Res. 25, 1751-1761.
113. Leoutsakos J. M., Muthen B. O., Breitner J. C., and, Lyketsos C. G., (2012) Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer's Disease Anti-inflammatory Prevention Trial. Int. J. Geriatr. Psychiatry 27, 364-374.
114. Lesne S. E., Sherman M. A., Grant M., Kuskowski M., Schneider J. A., Bennett D. A., and, Ashe K. H., (2013) Brain amyloid-beta oligomers in ageing and Alzheimer's disease. Brain 136, 1383-1398.
115. Li X., Shen N., Zhang S., et al,. (2014) CD33 rs3865444 polymorphism contributes to Alzheimer's disease susceptibility in Chinese, European, and North American populations. Mol. Neurobiol. doi: 10.1007/s12035-014-8880-9.
116. Lindberg C., Selenica M. L., Westlind-Danielsson A., and, Schultzberg M., (2005) Beta-amyloid protein structure determines the nature of cytokine release from rat microglia. J. Mol. Neurosci. 27, 1-12.
117. Linton M. F., Gish R., Hubl S. T., Butler E., Esquivel C., Bry W. I., Boyles J. K., Wardell M. R., and, Young S. G., (1991) Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation. J. Clin. Invest. 88, 270-281.
118. Liu C. C., Kanekiyo T., Xu H., and, Bu G., (2013) Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat. Rev. Neurol. 9, 106-118.
119. Liu Y. H., Wang Y. R., Xiang Y., Zhou H. D., Giunta B., Manucat-Tan N. B., Tan J., Zhou X. F., and, Wang Y. J., (2014) Clearance of amyloid-beta in Alzheimer's disease: shifting the action site from center to periphery. Mol. Neurobiol. 51, 1-7.
120. Lue L. F., Kuo Y. M., Roher A. E., et al,. (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am. J. Pathol. 155, 853-862.
121. Lue L. F., Schmitz C., and, Walker D. G., (2014) What happens to microglial TREM2 in Alzheimer's disease: immunoregulatory turned into immunopathogenic? Neuroscience doi: 10.1016/j.neuroscience.2014.09.050.
122. Lyketsos C. G., Breitner J. C., Green R. C., Martin B. K., Meinert C., Piantadosi S., and, Sabbagh M., (2007) Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology 68, 1800-1808.
123. Ma L., Dong F., Zaid M., Kumar A., and, Zha X., (2012) ABCA1 protein enhances Toll-like receptor 4 (TLR4)-stimulated interleukin-10 (IL-10) secretion through protein kinase A (PKA) activation. J. Biol. Chem. 287, 40502-40512.
124. Maezawa I., Maeda N., Montine T. J., and, Montine K. S., (2006a) Apolipoprotein E-specific innate immune response in astrocytes from targeted replacement mice. J. Neuroinflammation 3, 10.
125. Maezawa I., Nivison M., Montine K. S., Maeda N., and, Montine T. J., (2006b) Neurotoxicity from innate immune response is greatest with targeted replacement of E4 allele of apolipoprotein E gene and is mediated by microglial p38MAPK. FASEB J. 20, 797-799.
126. Maezawa I., Zaja-Milatovic S., Milatovic D., Stephen C., Sokal I., Maeda N., Montine T. J., and, Montine K. S., (2006c) Apolipoprotein E isoform-dependent dendritic recovery of hippocampal neurons following activation of innate immunity. J. Neuroinflammation 3, 21.
127. Mahley R. W., and, Ji Z. S., (1999) Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E. J. Lipid Res. 40, 1-16.
128. Mahley R. W., Weisgraber K. H., and, Huang Y., (2009) Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS. J. Lipid Res. 50 (Suppl), S183-S188.
129. Malm T. M., Koistinaho M., Parepalo M., Vatanen T., Ooka A., Karlsson S., and, Koistinaho J., (2005) Bone-marrow-derived cells contribute to the recruitment of microglial cells in response to beta-amyloid deposition in APP/PS1 double transgenic Alzheimer mice. Neurobiol. Dis. 18, 134-142.
130. Mantovani A., Sozzani S., Locati M., Allavena P., and, Sica A., (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 23, 549-555.
131. Mantovani A., Sica A., Sozzani S., Allavena P., Vecchi A., and, Locati M., (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 25, 677-686.
132. Martin B. K., Meinert C. L., and, Breitner J. C., (2002) Double placebo design in a prevention trial for Alzheimer's disease. Control. Clin. Trials 23, 93-99.
133. Martin B. K., Szekely C., Brandt J., Piantadosi S., Breitner J. C., Craft S., Evans D., Green R., and, Mullan M., (2008) Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib. Arch. Neurol. 65, 896-905.
134. Martinez-Morillo E., Hansson O., Atagi Y., Bu G., Minthon L., Diamandis E. P., and, Nielsen H. M., (2014) Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls. Acta Neuropathol. 127, 633-643.
135. McGeer P. L., and, McGeer E. G., (2013) The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol. 126, 479-497.
136. McLean C. A., Cherny R. A., Fraser F. W., Fuller S. J., Smith M. J., Beyreuther K., Bush A. I., and, Masters C. L., (1999) Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann. Neurol. 46, 860-866.
137. Medeiros R., and, LaFerla F. M., (2013) Astrocytes: conductors of the Alzheimer disease neuroinflammatory symphony. Exp. Neurol. 239, 133-138.
138. Meinert C. L., McCaffrey L. D., and, Breitner J. C., (2009) Alzheimer's Disease Anti-Inflammatory Prevention Trial: design, methods, and baseline results. Alzheimers Dement. 5, 93-104.
139. Meraz-Rios M. A., Toral-Rios D., Franco-Bocanegra D., Villeda-Hernandez J., and, Campos-Pena V., (2013) Inflammatory process in Alzheimer's disease. Front. Integr. Neurosci. 7, 59.
140. Michaelson D. M., (2014) ApoE4: the most prevalent yet understudied risk factor for Alzheimer's disease. Alzheimers Dement. 10, 861-868.
141. Michaud J. P., Halle M., Lampron A., et al,. (2013) Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer's disease-related pathology. Proc. Natl Acad. Sci. USA 110, 1941-1946.
142. Minoretti P., Gazzaruso C., Vito C. D., Emanuele E., Bianchi M., Coen E., Reino M., and, Geroldi D., (2006) Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer's disease. Neurosci. Lett. 391, 147-149.
143. Mistry M. J., Clay M. A., Kelly M. E., Steiner M. A., and, Harmony J. A., (1995) Apolipoprotein E restricts interleukin-dependent T lymphocyte proliferation at the G1A/G1B boundary. Cell. Immunol. 160, 14-23.
144. Mohamed A., and, Posse de Chaves E., (2011) Aβ internalization by neurons and glia. Int. J. Alzheimers Dis. 2011, 127984.
145. Mosser D. M., and, Edwards J. P., (2008) Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8, 958-969.
146. Munder M., (2009) Arginase: an emerging key player in the mammalian immune system. Br. J. Pharmacol. 158, 638-651.
147. Naj A. C., Jun G., Beecham G. W., et al,. (2011) Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat. Genet. 43, 436-441.
148. Nuzzo D., Picone P., Caruana L., Vasto S., Barera A., Caruso C., and, Di Carlo M., (2014) Inflammatory mediators as biomarkers in brain disorders. Inflammation 37, 639-648.
149. Nwabuisi-Heath E., LaDu M. J., and, Yu C., (2012) Simultaneous analysis of dendritic spine density, morphology and excitatory glutamate receptors during neuron maturation in vitro by quantitative immunocytochemistry. J. Neurosci. Methods 207, 137-147.
150. Oakley H., Cole S. L., Logan S., et al,. (2006) Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation. J. Neurosci. 26, 10129-10140.
151. Okun E., Griffioen K. J., Lathia J. D., Tang S. C., Mattson M. P., and, Arumugam T. V., (2009) Toll-like receptors in neurodegeneration. Brain Res. Rev. 59, 278-292.
152. Okun E., Griffioen K. J., and, Mattson M. P., (2011) Toll-like receptor signaling in neural plasticity and disease. Trends Neurosci. 34, 269-281.
153. Opal S. M., Laterre P. F., Francois B., et al,. (2013) Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA 309, 1154-1162.
154. Parvathy S., Rajadas J., Ryan H., Vaziri S., Anderson L., and, Murphy G. M., Jr, (2009) Aβ peptide conformation determines uptake and interleukin-1alpha expression by primary microglial cells. Neurobiol. Aging 30, 1792-1804.
155. Peri F., and, Piazza M., (2012) Therapeutic targeting of innate immunity with Toll-like receptor 4 (TLR4) antagonists. Biotechnol. Adv. 30, 251-260.
156. Perlmutter L. S., Barron E., and, Chui H. C., (1990) Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease. Neurosci. Lett. 119, 32-36.
157. Pernot F., Dorandeu F., Beaup C., and, Peinnequin A., (2010) Selection of reference genes for real-time quantitative reverse transcription-polymerase chain reaction in hippocampal structure in a murine model of temporal lobe epilepsy with focal seizures. J. Neurosci. Res. 88, 1000-1008.
158. Persson M., Brantefjord M., Hansson E., and, Ronnback L., (2005) Lipopolysaccharide increases microglial GLT-1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF-alpha. Glia 51, 111-120.
159. Phillips M. C., (2014) Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB Life 66, 616-623.
160. Pocivavsek A., Burns M. P., and, Rebeck G. W., (2009a) Low-density lipoprotein receptors regulate microglial inflammation through c-Jun N-terminal kinase. Glia 57, 444-453.
161. Pocivavsek A., Mikhailenko I., Strickland D. K., and, Rebeck G. W., (2009b) Microglial low-density lipoprotein receptor-related protein 1 modulates c-Jun N-terminal kinase activation. J. Neuroimmunol. 214, 25-32.
162. Prinz M., and, Priller J., (2014) Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat. Rev. Neurosci. 15, 300-312.
163. Qiu W. Q., Mwamburi M., Besser L. M., et al,. (2013) Angiotensin converting enzyme inhibitors and the reduced risk of Alzheimer's disease in the absence of apolipoprotein E4 allele. J. Alzheimers Dis. 37, 421-428.
164. Quinn J., Montine T., Morrow J., Woodward W. R., Kulhanek D., and, Eckenstein F., (2003) Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease. J. Neuroimmunol. 137, 32-41.
165. Ratthe C., Pelletier M., Chiasson S., and, Girard D., (2007) Molecular mechanisms involved in interleukin-4-induced human neutrophils: expression and regulation of suppressor of cytokine signaling. J. Leukoc. Biol. 81, 1287-1296.
166. Reyes T. M., Fabry Z., and, Coe C. L., (1999) Brain endothelial cell production of a neuroprotective cytokine, interleukin-6, in response to noxious stimuli. Brain Res. 851, 215-220.
167. Riddell D. R., Zhou H., Atchison K., et al,. (2008) Impact of apolipoprotein E (ApoE) polymorphism on brain ApoE levels. J. Neurosci. 28, 11445-11453.
168. Risner M. E., Saunders A. M., Altman J. F., Ormandy G. C., Craft S., Foley I. M., Zvartau-Hind M. E., Hosford D. A., and, Roses A. D., (2006) Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J 6, 246-254.
169. Rodriguez G. A., Tai L. M., LaDu M. J., and, Rebeck G. W., (2014) Human APOE4 increases microglia reactivity at Aβ plaques in a mouse model of Abeta deposition. J. Neuroinflammation 11, 111.
170. Roselaar S. E., and, Daugherty A., (1998) Apolipoprotein E-deficient mice have impaired innate immune responses to Listeria monocytogenes in vivo. J. Lipid Res. 39, 1740-1743.
171. Rosenberg G. A., (2002) Matrix metalloproteinases in neuroinflammation. Glia 39, 279-291.
172. Ross J., Sharma S., Winston J., et al,. (2013) CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study. Curr. Alzheimer Res. 10, 742-753.
173. Rubio-Perez J. M., and, Morillas-Ruiz J. M., (2012) A review: inflammatory process in Alzheimer's disease, role of cytokines. ScientificWorldJournal 2012, 756357.
174. Russo I., Barlati S., and, Bosetti F., (2011) Effects of neuroinflammation on the regenerative capacity of brain stem cells. J. Neurochem. 116, 947-956.
175. Sardi F., Fassina L., Venturini L., Inguscio M., Guerriero F., Rolfo E., and, Ricevuti G., (2011) Alzheimer's disease, autoimmunity and inflammation. The good, the bad and the ugly. Autoimmun. Rev. 11, 149-153.
176. Sebollela A., Mustata G. M., Luo K., et al,. (2014) Elucidating molecular mass and shape of a neurotoxic Aβ oligomer. ACS Chem. Neurosci. 5, 1238-1245.
177. Selkoe D. J., (2011) Resolving controversies on the path to Alzheimer's therapeutics. Nat. Med. 17, 1060-1065.
178. Shen Y., Yang L., and, Li R., (2013) What does complement do in Alzheimer's disease? Old molecules with new insights. Transl. Neurodegener. 2, 21.
179. Sheng J. G., Bora S. H., Xu G., Borchelt D. R., Price D. L., and, Koliatsos V. E., (2003) Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid beta peptide in APPswe transgenic mice. Neurobiol. Dis. 14, 133-145.
180. Shimizu E., Kawahara K., Kajizono M., Sawada M., and, Nakayama H., (2008) IL-4-induced selective clearance of oligomeric beta-amyloid peptide(1-42) by rat primary type 2 microglia. J. Immunol. 181, 6503-6513.
181. Simard A. R., Soulet D., Gowing G., Julien J. P., and, Rivest S., (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 49, 489-502.
182. Skerrett R., Malm T., and, Landreth G., (2014) Nuclear receptors in neurodegenerative diseases. Neurobiol. Dis. 72 (Pt A), 104-116.
183. Soares H. D., Potter W. Z., Pickering E., et al,. (2012) Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease. Arch. Neurol. 69, 1310-1317.
184. Sola C., Casal C., Tusell J. M., and, Serratosa J., (2002) Astrocytes enhance lipopolysaccharide-induced nitric oxide production by microglial cells. Eur. J. Neurosci. 16, 1275-1283.
185. Solomon S. D., McMurray J. J., Pfeffer M. A., et al,. (2005) Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N. Engl. J. Med. 352, 1071-1080.
186. Sondag C. M., Dhawan G., and, Combs C. K., (2009) Beta amyloid oligomers and fibrils stimulate differential activation of primary microglia. J. Neuroinflammation 6, 1.
187. Song M., Jin J., Lim J. E., et al,. (2011) TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's disease. J. Neuroinflammation 8, 92.
188. Sperling R. A., Jack C. R., Jr, Black S. E., et al,. (2011) Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup. Alzheimers Dement. 7, 367-385.
189. Sperling R., Salloway S., Brooks D. J., et al,. (2012) Amyloid-related imaging abnormalities in patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol. 11, 241-249.
190. Spillmann F., Van Linthout S., Miteva K., Lorenz M., Stangl V., Schultheiss H. P., and, Tschope C., (2014) LXR agonism improves TNF-alpha-induced endothelial dysfunction in the absence of its cholesterol-modulating effects. Atherosclerosis 232, 1-9.
191. Stine W. B., Jr, Dahlgren K. N., Krafft G. K., and, LaDu M. J., (2003) In vitro characterization of conditions for amyloid-beta peptide oligomerization and fibrillogenesis. J. Biol. Chem. 278, 11612-11622.
192. Sullivan P. M., Mezdour H., Aratani Y., Knouff C., Najib J., Reddick R. L., Quarfordt S. H., and, Maeda N., (1997) Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis. J. Biol. Chem. 272, 17972-17980.
193. Sullivan P. M., Mezdour H., Quarfordt S. H., and, Maeda N., (1998) Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe∗2. J. Clin. Invest. 102, 130-135.
194. Sullivan P. M., Han B., Liu F., Mace B. E., Ervin J. F., Wu S., Koger D., Paul S., and, Bales K. R., (2011) Reduced levels of human apoE4 protein in an animal model of cognitive impairment. Neurobiol. Aging 32, 791-801.
195. Swijsen A., Nelissen K., Janssen D., Rigo J. M., and, Hoogland G., (2012) Validation of reference genes for quantitative real-time PCR studies in the dentate gyrus after experimental febrile seizures. BMC Res. Notes 5, 685.
196. Tahara K., Kim H. D., Jin J. J., Maxwell J. A., Li L., and, Fukuchi K., (2006) Role of toll-like receptor signalling in Aβ uptake and clearance. Brain 129, 3006-3019.
197. Tai L. M., Youmans K. L., Jungbauer L., Yu C., and, Ladu M. J., (2011) Introducing human APOE into Aβ transgenic mouse models. Int. J. Alzheimers Dis. 2011, 810981.
198. Tai L. M., Bilousova T., Jungbauer L., et al,. (2013) Levels of soluble apolipoprotein E/amyloid-beta (Aβ) complex are reduced and oligomeric Aβ increased with APOE4 and Alzheimer disease in a transgenic mouse model and human samples. J. Biol. Chem. 288, 5914-5926.
199. Tai L. M., Koster K. P., Luo J., Lee S. H., Wang Y. T., Collins N. C., Ben Aissa M., Thatcher G. R., and, LaDu M. J., (2014a) Amyloid-beta pathology and APOE genotype modulate retinoid X receptor agonist activity in vivo. J. Biol. Chem. 289, 30538-30555.
200. Tai L. M., Mehra S., Shete V., Estus S., Rebeck G. W., Bu G., and, Ladu M. J., (2014b) Soluble apoE/Aβ complex: mechanism and therapeutic target for APOE4-induced AD risk. Mol. Neurodegener. 9, 2.
201. Tang S. C., Lathia J. D., Selvaraj P. K., et al,. (2008) Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal. Exp. Neurol. 213, 114-121.
202. Tarassishin L., Suh H. S., and, Lee S. C., (2014) LPS and IL-1 differentially activate mouse and human astrocytes: role of CD14. Glia 62, 999-1013.
203. Teplow D. B., (2013) On the subject of rigor in the study of amyloid beta-protein assembly. Alzheimers Res. Ther. 5, 39.
204. Thal D. R., Capetillo-Zarate E., Del Tredici K., and, Braak H., (2006) The development of amyloid beta protein deposits in the aged brain. Sci. Aging Knowledge Environ. 2006, re1.
205. Thal D. R., Griffin W. S., and, Braak H., (2008) Parenchymal and vascular Aβ-deposition and its effects on the degeneration of neurons and cognition in Alzheimer's disease. J. Cell Mol. Med. 12, 1848-1862.
206. Tilleux S., and, Hermans E., (2007) Neuroinflammation and regulation of glial glutamate uptake in neurological disorders. J. Neurosci. Res. 85, 2059-2070.
207. Tobinick E., (2009) Tumour necrosis factor modulation for treatment of Alzheimer's disease: rationale and current evidence. CNS Drugs 23, 713-725.
208. Tomic J. L., Pensalfini A., Head E., and, Glabe C. G., (2009) Soluble fibrillar oligomer levels are elevated in Alzheimer's disease brain and correlate with cognitive dysfunction. Neurobiol. Dis. 35, 352-358.
209. Ulevitch R. J., and, Tobias P. S., (1999) Recognition of gram-negative bacteria and endotoxin by the innate immune system. Curr. Opin. Immunol. 11, 19-22.
210. Vadeboncoeur N., Segura M., Al-Numani D., Vanier G., and, Gottschalk M., (2003) Pro-inflammatory cytokine and chemokine release by human brain microvascular endothelial cells stimulated by Streptococcus suis serotype 2. FEMS Immunol. Med. Microbiol. 35, 49-58.
211. Van Eldik L. J., Thompson W. L., Ralay Ranaivo H., Behanna H. A., and, Martin Watterson D., (2007) Glia proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: function-based and target-based discovery approaches. Int. Rev. Neurobiol. 82, 277-296.
212. Verghese P. B., Castellano J. M., and, Holtzman D. M., (2011) Apolipoprotein E in Alzheimer's disease and other neurological disorders. Lancet Neurol. 10, 241-252.
213. Vitek M. P., Brown C. M., and, Colton C. A., (2009) APOE genotype-specific differences in the innate immune response. Neurobiol. Aging 30, 1350-1360.
214. Vitek M. P., Christensen D. J., Wilcock D., Davis J., Van Nostrand W. E., Li F. Q., and, Colton C. A., (2012) APOE-mimetic peptides reduce behavioral deficits, plaques and tangles in Alzheimer's disease transgenics. Neurodegener. Dis. 10, 122-126.
215. de Vries H. E., Blom-Roosemalen M. C., van Oosten M., de Boer A. G., van Berkel T. J., Breimer D. D., and, Kuiper J., (1996) The influence of cytokines on the integrity of the blood-brain barrier in vitro. J. Neuroimmunol. 64, 37-43.
216. de Vries H. E., Kuiper J., de Boer A. G., Van Berkel T. J., and, Breimer D. D., (1997) The blood-brain barrier in neuroinflammatory diseases. Pharmacol. Rev. 49, 143-155.
217. Wahrle S. E., Jiang H., Parsadanian M., Legleiter J., Han X., Fryer J. D., Kowalewski T., and, Holtzman D. M., (2004) ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE. J. Biol. Chem. 279, 40987-40993.
218. Walter S., Letiembre M., Liu Y., et al,. (2007) Role of the toll-like receptor 4 in neuroinflammation in Alzheimer's disease. Cell. Physiol. Biochem. 20, 947-956.
219. Wang J., Dickson D. W., Trojanowski J. Q., and, Lee V. M., (1999) The levels of soluble versus insoluble brain Aβ distinguish Alzheimer's disease from normal and pathologic aging. Exp. Neurol. 158, 328-337.
220. Wang L. Z., Yu J. T., Miao D., Wu Z. C., Zong Y., Wen C. Q., and, Tan L., (2011) Genetic association of TLR4/11367 polymorphism with late-onset Alzheimer's disease in a Han Chinese population. Brain Res. 1381, 202-207.
221. Watterson D. M., Grum-Tokars V. L., Roy S. M., et al,. (2013) Development of novel chemical probes to address CNS protein kinase involvement in synaptic dysfunction. PLoS ONE 8, e66226.
222. Weisgraber K. H., Innerarity T. L., and, Mahley R. W., (1982) Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site. J. Biol. Chem. 257, 2518-2521.
223. White J. A., Manelli A. M., Holmberg K. H., Van Eldik L. J., and, LaDu M. J., (2005) Differential effects of oligomeric and fibrillar amyloid-beta1-42 on astrocyte-mediated inflammation. Neurobiol. Dis. 18, 459-465.
224. Wilcock D. M., and, Griffin W. S., (2013) Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis. J. Neuroinflammation 10, 84.
225. Wozniak M. A., Itzhaki R. F., Faragher E. B., James M. W., Ryder S. D., Irving W. L., and, Trent H. C. V. S. G., (2002) Apolipoprotein E-epsilon 4 protects against severe liver disease caused by hepatitis C virus. Hepatology 36, 456-463.
226. Wyss-Coray T., and, Rogers J., (2012) Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb. Perspect Med. 2, a006346.
227. Xing B., Bachstetter A. D., and, Van Eldik L. J., (2011) Microglial p38alpha MAPK is critical for LPS-induced neuron degeneration, through a mechanism involving TNFalpha. Mol. Neurodegener. 6, 84.
228. Xu J., Storer P. D., Chavis J. A., Racke M. K., and, Drew P. D., (2005) Agonists for the peroxisome proliferator-activated receptor-alpha and the retinoid X receptor inhibit inflammatory responses of microglia. J. Neurosci. Res. 81, 403-411.
229. Xu Q., Bernardo A., Walker D., Kanegawa T., Mahley R. W., and, Huang Y., (2006) Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locus. J. Neurosci. 26, 4985-4994.
230. Yang Y., Cudaback E., Jorstad N. L., et al,. (2013) APOE3, but not APOE4, bone marrow transplantation mitigates behavioral and pathological changes in a mouse model of Alzheimer disease. Am. J. Pathol. 183, 905-917.
231. Youmans K. L., Tai L. M., Nwabuisi-Heath E., et al,. (2012) APOE4-specific changes in Aβ accumulation in a new transgenic mouse model of Alzheimer disease. J. Biol. Chem. 287, 41774-41786.
232. Yu Y., and, Ye R. D., (2014) Microglial Aβ receptors in Alzheimer's disease. Cell. Mol. Neurobiol. 35, 71-83.
233. Yu J. T., Miao D., Cui W. Z., Ou J. R., Tian Y., Wu Z. C., Zhang W., and, Tan L., (2012) Common variants in toll-like receptor 4 confer susceptibility to Alzheimer's disease in a Han Chinese population. Curr. Alzheimer Res. 9, 458-466.
234. Zelcer N., Khanlou N., Clare R., Jiang Q., Reed-Geaghan E. G., Landreth G. E., Vinters H. V., and, Tontonoz P., (2007) Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors. Proc. Natl Acad. Sci. USA 104, 10601-10606.
235. Zhao L., Lin S., Bales K. R., et al,. (2009) Macrophage-mediated degradation of beta-amyloid via an apolipoprotein E isoform-dependent mechanism. J. Neurosci. 29, 3603-3612.
236. Zhu Y., Nwabuisi-Heath E., Dumanis S. B., Tai L. M., Yu C., Rebeck G. W., and, LaDu M. J., (2012) APOE genotype alters glial activation and loss of synaptic markers in mice. Glia 60, 559-569.