CD45 deficiency drives amyloid-β peptide oligomers and neuronal loss in alzheimer's disease mice

Journal of Neuroscience

Volumn 31, Issue 4, 2011, Pages 1355-1365

  Zhu, Yuyan ^a,b   Hou, Huayan ^a   Rezai Zadeh, Kavon ^e   Giunta, Brian ^a,b   Ruscin, Amanda ^a,b   Gemma, Carmelina ^c   Jin, JingJi ^a,b   Dragicevic, Natasa ^a   Bradshaw, Patrick ^a   Rasool, Suhail ^g   Glabe, Charles G ^g   Ehrhart, Jared ^a,b   Bickford, Paula ^c,d   Mori, Takashi ^h   Obregon, Demian ^a,b   Town, Terrence ^e,f,i   Tan, Jun ^a,b,d  

^a UNIVERSITY OF SOUTH FLORIDA   (United States)

^b UNIVERSITY OF SOUTH FLORIDA   (United States)

^c Departments of Neurosurgery and Brain Repair   (United States)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

^e Regenerative Medicine Institute   (United States)

^f CEDARS SINAI MEDICAL CENTER   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

^h SAITAMA MEDICAL UNIVERSITY   (Japan)

ⁱ UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; CASPASE 3; CD45 ANTIGEN; INTERLEUKIN 1BETA; PRESENILIN 1; PROTEIN BAX; PROTEIN BCL XL; TUMOR NECROSIS FACTOR ALPHA;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BRAIN CORTEX; CELL ACTIVATION; CELL LOSS; CONTROLLED STUDY; CYTOKINE RELEASE; DISEASE ASSOCIATION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENZYME ACTIVATION; FEMALE; IMMUNE DEFICIENCY; LEUKOCYTE COMMON ANTIGEN DEFICIENCY; MICROGLIA; MOUSE; NERVE CELL; NERVE CELL LESION; NEURONAL LOSS; NEUROPATHOLOGY; NEUROTOXICITY; NONHUMAN; PHAGOCYTOSIS; PHENOTYPE; PRIORITY JOURNAL; TRANSGENE;

AGING; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOIDOSIS; ANIMALS; ANTIGENS, CD45; BLOOD-BRAIN BARRIER; CELLS, CULTURED; CEREBRAL CORTEX; HUMANS; INFLAMMATION; INTERLEUKIN-1BETA; MICE; MICE, MUTANT STRAINS; MICE, TRANSGENIC; MICROGLIA; MITOCHONDRIA; NEURONS; PEPTIDE FRAGMENTS; PRESENILIN-1; PROTEIN MULTIMERIZATION; TRANSGENES; TUMOR NECROSIS FACTOR-ALPHA;

EID: 79251560289     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.3268-10.2011     Document Type: Article

References (87)

1. Ahmed Z, Shaw G, Sharma VP, Yang C, McGowan E, Dickson DW (2007) Actin-binding proteins coronin-1a and IBA-1 are effective microglial markers for immunohistochemistry. J Histochem Cytochem 55:687-700. (Pubitemid 46981767)
2. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, et al. (2000) Inflammation and Alzheimer's disease. Neurobiol Aging 21:383-421.
3. Allsop D, Haga SI, Haga C, Ikeda SI, Mann DM, Ishii T (1989) Early senile plaques in Down's syndrome brains show a close relationship with cell bodies of neurons. Neuropathol Appl Neurobiol 15:531-542.
4. Bard F, Cannon C, Barbour R, Burke RL, Games D, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Lieberburg I, Motter R, Nguyen M, Soriano F, Vasquez N, Weiss K, Welch B, Seubert P, Schenk D, Yednock T (2000) Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 6:916-919.
5. Barger SW, Harmon AD (1997) Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature 388:878-881.
6. Benatar T, Carsetti R, Furlonger C, Kamalia N, Mak T, Paige CJ (1996) Immunoglobulin-mediated signal transduction in B cells from CD45-deficient mice. J Exp Med 183:329-334.
7. Benzing WC, Wujek JR, Ward EK, Shaffer D, Ashe KH, Younkin SG, Brunden KR (1999) Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice. Neurobiol Aging 20:581-589. (Pubitemid 30064403)
8. Carson MJ, Reilly CR, Sutcliffe JG, Lo D (1998) Mature microglia resemble immature antigen-presenting cells. Glia 22:72-85. (Pubitemid 28038045)
9. Chung H, Brazil MI, Soe TT, Maxfield FR (1999) Uptake, degradation, and release of fibrillar and soluble forms of Alzheimer's amyloid beta-peptide by microglial cells. J Biol Chem 274:32301-32308.
10. Colton CA (2009) Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 4:399-418.
11. Colton CA, Wilcock DM (2010) Assessing activation states in microglia. CNS Neurol Disord Drug Targets 9:174-191.
12. Cottrell DA, Blakely EL, Johnson MA, Ince PG, Turnbull DM (2001) Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD. Neurology 57:260-264.
13. Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E, Welch D, Manness L, Lin C, Yu J, Zhu H, Ghiso J, Frangione B, Stern A, Schmidt AM, Armstrong DL, Arnold B, Liliensiek B, Nawroth P, Hofman F, Kindy M, Stern D, Zlokovic B (2003) RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 9:907-913.
14. DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM (2001) Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 98:8850-8855.
15. DeMattos RB, Bales KR, Cummins DJ, Paul SM, Holtzman DM (2002) Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease. Science 295:2264-2267. (Pubitemid 34258840)
16. El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13:432-438. (Pubitemid 46559828)
17. Familian A, Eikelenboom P, Veerhuis R (2007) Minocycline does not affect amyloid beta phagocytosis by human microglial cells. Neurosci Lett 416:87-91.
18. Frackowiak J, Wisniewski HM, Wegiel J, Merz GS, Iqbal K, Wang KC (1992) Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils. Acta Neuropathol 84:225-233.
19. Frautschy SA, Yang F, Calderón L, Cole GM (1996) Rodent models of Alzheimer's disease: rat A beta infusion approaches to amyloid deposits. Neurobiol Aging 17:311-321.
20. Fuhrmann M, Bittner T, Jung CK, Burgold S, Page RM, Mitteregger G, Haass C, LaFerla FM, Kretzschmar H, Herms J (2010) Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nat Neurosci 13:411-413.
21. Fukui H, Diaz F, Garcia S, Moraes CT (2007) Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 104:14163-14168.
22. Glabe CG (2008) Structural classification of toxic amyloid oligomers. J Biol Chem 283:29639-29643.
23. Grathwohl SA, Kälin RE, Bolmont T, Prokop S, Winkelmann G, Kaeser SA, Odenthal J, Radde R, Eldh T, Gandy S, Aguzzi A, Staufenbiel M, Mathews PM, Wolburg H, Heppner FL, Jucker M (2009) Formation and maintenance of Alzheimer's disease beta-amyloid plaques in the absence of microglia. Nat Neurosci 12:1361-1363.
24. Green DA, Masliah E, Vinters HV, Beizai P, Moore DJ, Achim CL (2005) Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. AIDS 19:407-411.
25. Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci 12:383-388.
26. Heneka MT, O'Banion MK (2007) Inflammatory processes in Alzheimer's disease. J Neuroimmunol 184:69-91.
27. Irie-Sasaki J, Sasaki T, Matsumoto W, Opavsky A, Cheng M, Welstead G, Griffiths E, Krawczyk C, Richardson CD, Aitken K, Iscove N, Koretzky G, Johnson P, Liu P, Rothstein DM, Penninger JM (2001) CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling. Nature 409:349-354.
28. Ito S, Ohtsuki S, Terasaki T (2006) Functional characterization of the brain-to-blood efflux clearance of human amyloid-beta peptide (1-40) across the rat blood-brain barrier. Neurosci Res 56:246-252.
29. Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Borchelt DR (2001) Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng 17:157-165.
30. Jimenez S, Baglietto-Vargas D, Caballero C, Moreno-Gonzalez I, Torres M, Sanchez-Varo R, Ruano D, Vizuete M, Gutierrez A, Vitorica J (2008) Inflammatory response in the hippocampus of PS1M146L/APP751SL mouse model of Alzheimer's disease: age-dependent switch in the microglial phenotype from alternative to classic. J Neurosci 28:11650 -11661.
31. Justement LB (1997) The role of CD45 in signal transduction. Adv Immunol 66:1-65.
32. Kayed R, Head E, Sarsoza F, Saing T, Cotman CW, Necula M, Margol L, Wu J, Breydo L, Thompson JL, Rasool S, Gurlo T, Butler P, Glabe CG (2007) Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol Neurodegener 2:18.
33. Klyubin I, Walsh DM, Lemere CA, Cullen WK, Shankar GM, Betts V, Spooner ET, Jiang L, Anwyl R, Selkoe DJ, Rowan MJ (2005) Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo. Nat Med 11:556-561.
34. Koo EH, Squazzo SL (1994) Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J Biol Chem 269:17386-17389.
35. Lesné S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440:352-357.
36. Licastro F, Mallory M, Hansen LA, Masliah E (1998) Increased levels of alpha-1-antichymotrypsin in brains of patients with Alzheimer's disease correlate with activated astrocytes and are affected by APOE 4 genotype. J Neuroimmunol 88:105-110.
37. Lim GP, Yang F, Chu T, Chen P, Beech W, Teter B, Tran T, Ubeda O, Ashe KH, Frautschy SA, Cole GM (2000) Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J Neurosci 20:5709-5714.
38. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21:8370-8377.
39. Maier M, Peng Y, Jiang L, Seabrook TJ, Carroll MC, Lemere CA (2008) Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice. J Neurosci 28:6333-6341.
40. Mancuso M, Orsucci D, Siciliano G, Murri L (2008) Mitochondria, mitochondrial DNA and Alzheimer's disease. What comes first? Curr Alzheimer Res 5:457-468.
41. Mandrekar-Colucci S, Landreth GE (2010) Microglia and inflammation in Alzheimer's disease. CNS Neurol Disord Drug Targets 9:156-167.
42. Martel CL, Mackic JB, Matsubara E, Governale S, Miguel C, Miao W, Mc-Comb JG, Frangione B, Ghiso J, Zlokovic BV (1997) Isoform-specific effects of apolipoproteins E2, E3, and E4 on cerebral capillary sequestration and blood-brain barrier transport of circulating Alzheimer's amyloid beta. J Neurochem 69:1995-2004.
43. Martin LJ, Pardo CA, Cork LC, Price DL (1994) Synaptic pathology and glial responses to neuronal injury precede the formation of senile plaques and amyloid deposits in the aging cerebral cortex. Am J Pathol 145:1358-1381.
44. Masliah E, Mallory M, Hansen L, Alford M, Albright T, Terry R, Shapiro P, Sundsmo M, Saitoh T (1991) Immunoreactivity of CD45, a protein phosphotyrosine phosphatase, in Alzheimer's disease. Acta Neuropathol 83:12-20.
45. McGeer PL, Itagaki S, Tago H, McGeer EG (1987) Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 79:195-200.
46. Meda L, Cassatella MA, Szendrei GI, Otvos L Jr, Baron P, Villalba M, Ferrari D, Rossi F (1995) Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature 374:647-650.
47. Mildner A, Schmidt H, Nitsche M, Merkler D, Hanisch UK, Mack M, Heikenwalder M, Brück W, Priller J, Prinz M (2007) Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat Neurosci 10:1544 -1553.
48. Mitrasinovic OM, Murphy GM Jr (2002) Accelerated phagocytosis of amyloid-beta by mouse and human microglia overexpressing the macrophage colony-stimulating factor receptor. J Biol Chem 277:29889-29896.
49. Parsadanian AS, Cheng Y, Keller-Peck CR, Holtzman DM, Snider WD (1998) Bcl-xL is an antiapoptotic regulator for postnatal CNS neurons. J Neurosci 18:1009-1019.
50. Penninger JM, Irie-Sasaki J, Sasaki T, Oliveira-dos-Santos AJ (2001) CD45: new jobs for an old acquaintance. Nat Immunol 2:389-396.
51. Probst A, Langui D, Ipsen S, Robakis N, Ulrich J (1991) Deposition of beta/ A4 protein along neuronal plasma membranes in diffuse senile plaques. Acta Neuropathol 83:21-29.
52. Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, Ehrhart J, Townsend K, Zeng J, Morgan D, Hardy J, Town T, Tan J (2005) Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci 25:8807-8814.
53. Roach T, Slater S, Koval M, White L, Cahir McFarland ED, Okumura M, Thomas M, Brown E (1997) CD45 regulates Src family member kinase activity associated with macrophage integrin-mediated adhesion. Curr Biol 7:408-417.
54. Saura J, Tusell JM, Serratosa J (2003) High-yield isolation of murine microglia by mild trypsinization. Glia 44:183-189.
55. Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, Walker S, Wogulis M, Yednock T, Games D, Seubert P (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173-177.
56. Sedgwick JD, Schwender S, Imrich H, Dörries R, Butcher GW, ter Meulen V (1991) Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc Natl Acad Sci U S A 88:7438-7442.
57. Selkoe DJ (2001) Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 81:741-766.
58. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 14:837-842.
59. Shenoi H, Seavitt J, Zheleznyak A, Thomas ML, Brown EJ (1999) Regulation of integrin-mediated T cell adhesion by the transmembrane protein tyrosine phosphatase CD45. J Immunol 162:7120-7127.
60. Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Frangione B, Holtzman DM, Miller CA, Strickland DK, Ghiso J, Zlokovic BV (2000) Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 106:1489-1499.
61. 1-40 clearance from the brain. J Neurosci 24:9632-9637.
62. Shoji M, Golde TE, Ghiso J, Cheung TT, Estus S, Shaffer LM, Cai XD, McKay DM, Tintner R, Frangione B (1992) Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science 258:126 -129.
63. Stibenz D, Buβhrer C, Laufer D, Obladen M (1996) CD45 engagement induces L-selectin down-regulation. Scand J Immunol 44:37-44.
64. Tan J, Town T, Paris D, Mori T, Suo Z, Crawford F, Mattson MP, Flavell RA, Mullan M (1999) Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation. Science 286:2352-2355.
65. Tan J, Town T, Mullan M (2000a) CD45 inhibits CD40L-induced microglial activation via negative regulation of the Src/p44/42 MAPK pathway. J Biol Chem 275:37224-37231.
66. Tan J, Town T, Mori T, Wu Y, Saxe M, Crawford F, Mullan M (2000b) CD45 opposes β-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activated protein kinase. J Neurosci 20:7587-7594.
67. Tan J, Town T, Crawford F, Mori T, DelleDonne A, Crescentini R, Obregon D, Flavell RA, Mullan MJ (2002) Role of CD40 ligand in amyloidosis in transgenic Alzheimer's mice. Nat Neurosci 5:1288-1293.
68. Terasaki T, Ohtsuki S (2005) Brain-to-blood transporters for endogenous substrates and xenobiotics at the blood-brain barrier: an overview of biology and methodology. NeuroRx 2:63-72.
69. Thomas ML, Brown EJ (1999) Positive and negative regulation of Srcfamily membrane kinases by CD45. Immunol Today 20:406-411.
70. Town T, Nikolic V, Tan J (2005) The microglial "activation" continuum: from innate to adaptive responses. J Neuroinflammation 2:24.
71. Town T, Laouar Y, Pittenger C, Mori T, Szekely CA, Tan J, Duman RS, Flavell RA (2008) Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat Med 14:681-687.
72. Townsend KP, Vendrame M, Ehrhart J, Faza B, Zeng J, Town T, Tan J (2004) CD45 isoform RB as a molecular target to oppose lipopolysaccharide-induced microglial activation in mice. Neurosci Lett 362:26-30.
73. Townsend KP, Town T, Mori T, Lue LF, Shytle D, Sanberg PR, Morgan D, Fernandez F, Flavell RA, Tan J (2005) CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid beta-peptide. Eur J Immunol 35:901-910.
74. Walsh DM, Tseng BP, Rydel RE, Podlisny MB, Selkoe DJ (2000) The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain. Biochemistry 39:10831-10839.
75. Walsh DM, Klyubin I, Shankar GM, Townsend M, Fadeeva JV, Betts V, Podlisny MB, Cleary JP, Ashe KH, Rowan MJ, Selkoe DJ (2005) The role of cell-derived oligomers of Abeta in Alzheimer's disease and avenues for therapeutic intervention. Biochem Soc Trans 33:1087-1090.
76. Watson D, Castaño E, Kokjohn TA, Kuo YM, Lyubchenko Y, Pinsky D, Connolly ES Jr, Esh C, Luehrs DC, Stine WB, Rowse LM, Emmerling MR, Roher AE (2005) Physicochemical characteristics of soluble oligomeric Abeta and their pathologic role in Alzheimer's disease. Neurol Res 27:869-881.
77. Wengenack TM, Whelan S, Curran GL, Duff KE, Poduslo JF (2000) Quantitative histological analysis of amyloid deposition in Alzheimer's double transgenic mouse brain. Neuroscience 101:939-944.
78. Wenk GL (2003) Neuropathologic changes in Alzheimer's disease. J Clin Psychiatry 64 [Suppl 9]:7-10.
79. Wertkin AM, Turner RS, Pleasure SJ, Golde TE, Younkin SG, Trojanowski JQ, Lee VM (1993) Humanneurons derived from a teratocarcinoma cell line express solely the 695-amino acid amyloid precursor protein and produce intracellular beta-amyloid or A4 peptides. Proc Natl Acad Sci U S A 90:9513-9517.
80. West MJ, Slomianka L, Gundersen HJ (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482-497.
81. Wilcock DM, Gordon MN, Ugen KE, Gottschall PE, DiCarlo G, Dickey C, Boyett KW, Jantzen PT, Connor KE, Melachrino J, Hardy J, Morgan D (2001) Number of Abeta inoculations in APP+PS1 transgenic mice influences antibody titers, microglial activation, and congophilic plaque levels. DNA Cell Biol 20:731-736.
82. Wild-Bode C, Yamazaki T, Capell A, Leimer U, Steiner H, Ihara Y, Haass C (1997) Intracellular generation and accumulation of amyloid betapeptide terminating at amino acid 42. J Biol Chem 272:16085-16088.
83. Wisniewski HM, Frackowiak J (1998) Commentary to "Differences between the pathogenesis of senile plaques and congophilic angiopathy in Alzheimer disease" [J Neuropathol Exp Neurol (1997) 56:751-761]. J Neuropathol Exp Neurol 57:96-98.
84. Wroblewski M, Hamann A (1997) CD45-mediated signals can trigger shedding of lymphocyte L-selectin. Int Immunol 9:555-562.
85. Wyss-Coray T (2006) Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 12:1005-1015.
86. Xu H, Sweeney D, Wang R, Thinakaran G, Lo AC, Sisodia SS, Greengard P, Gandy S (1997) Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation. Proc Natl Acad Sci U S A 94:3748-3752.
87. Zhu Y, Hou H, Nikolic WV, Ehrhart J, Rrapo E, Bickford P, Giunta B, Tan J (2008) CD45RB is a novel molecular therapeutic target to inhibit Abeta peptide-induced microglial MAPK activation. PLoS One 3:e2135.