Microglial alterations in human Alzheimer's disease following Aβ42 immunization

Neuropathology and Applied Neurobiology

Volumn 37, Issue 5, 2011, Pages 513-524

  Zotova, Elina ^a   Holmes, C ^a,b   Johnston, D ^a   Neal, J W ^d   Nicoll, J A R ^a,c   Boche, D ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b MOORGREEN HOSPITAL   (United Kingdom)

^c SOUTHAMPTON GENERAL HOSPITAL   (United Kingdom)

^d CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Alzheimer's disease; Amyloid; Immunotherapy; Inflammation

Indexed keywords

AMYLOID BETA PROTEIN[1-42]; CHLORDANE; HLA DR ANTIGEN;

ADULT; AGED; ALZHEIMER DISEASE; ARTICLE; CONFOCAL MICROSCOPY; CONTROLLED STUDY; FEMALE; HUMAN; HUMAN TISSUE; IMMUNIZATION; IMMUNOHISTOCHEMISTRY; MALE; MICROGLIA; PHAGOCYTOSIS; PRIORITY JOURNAL; SURVIVAL; UPREGULATION;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; ALZHEIMER VACCINES; AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; ANTIGENS, CD; ANTIGENS, DIFFERENTIATION, MYELOMONOCYTIC; BRAIN; CLINICAL TRIALS, PHASE I AS TOPIC; FEMALE; HUMANS; IMMUNOHISTOCHEMISTRY; MALE; MICROGLIA; MICROSCOPY, CONFOCAL; MIDDLE AGED; PLAQUE, AMYLOID;

EID: 79959826755     PISSN: 03051846     EISSN: 13652990     Source Type: Journal    
DOI: 10.1111/j.1365-2990.2010.01156.x     Document Type: Article

References (55)

1. Graham DI, Lantos PL. Greenfield's Neuropathology 7th edn. London: Arnold, 2002.
2. Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992; 256: 184-5.
3. Selkoe DJ. Alzheimer's disease is a synaptic failure. Science 2002; 298: 789-91.
4. Lowe J, Mirra SS, Hyman BT, Dickson DW. Ageing and dementia. In Greenfield's Neuropathology 8th edn. Eds S Love, DN Louis, DW Ellison. London: Edward Arnold Ltd., 2008; 1031-152.
5. Braak H, Braak E. Neuropil threads occur in dendrites of tangle-bearing nerve cells. Neuropathol Appl Neurobiol 1988; 14: 39-44.
6. Small SA, Duff K. Linking Abeta and tau in late-onset Alzheimer's disease: a dual pathway hypothesis. Neuron 2008; 60: 534-42.
7. Sheng JG, Mrak RE, Griffin WS. Microglial interleukin-1 alpha expression in brain regions in Alzheimer's disease: correlation with neuritic plaque distribution. Neuropathol Appl Neurobiol 1995; 21: 290-301.
8. Sheng JG, Mrak RE, Griffin WS. Glial-neuronal interactions in Alzheimer disease: progressive association of IL-1alpha+ microglia and S100beta+ astrocytes with neurofibrillary tangle stages. J Neuropathol Exp Neurol 1997; 56: 285-90.
9. Boche D, Nicoll JA. The role of the immune system in clearance of abeta from the brain. Brain Pathol 2008; 18: 267-78.
10. Rogers J, Luber-Narod J, Styren SD, Civin WH. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer's disease. Neurobiol Aging 1988; 9: 339-49.
11. McGeer PL, Itagaki S, Tago H, McGeer EG. Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 1987; 79: 195-200.
12. McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 1988; 38: 1285-91.
13. Rozemuller JM, Eikelenboom P, Pals ST, Stam FC. Microglial cells around amyloid plaques in Alzheimer's disease express leucocyte adhesion molecules of the LFA-1 family. Neurosci Lett 1989; 101: 288-92.
14. Mattiace LA, Davies P, Yen SH, Dickson DW. Microglia in cerebellar plaques in Alzheimer's disease. Acta Neuropathol 1990; 80: 493-8.
15. Overmyer M, Helisalmi S, Soininen H, Laakso M, Riekkinen P Sr, Alafuzoff I. Reactive microglia in aging and dementia: an immunohistochemical study of postmortem human brain tissue. Acta Neuropathol 1999; 97: 383-92.
16. Wisniewski HM, Wegiel J, Wang KC, Kujawa M, Lach B. Ultrastructural studies of the cells forming amyloid fibers in classical plaques. Can J Neurol Sci 1989; 16: 535-42.
17. Wisniewski HM, Wegiel J, Wang KC, Lach B. Ultrastructural studies of the cells forming amyloid in the cortical vessel wall in Alzheimer's disease. Acta Neuropathol 1992; 84: 117-27.
18. Wisniewski HM, Barcikowska M, Kida E. Phagocytosis of beta/A4 amyloid fibrils of the neuritic neocortical plaques. Acta Neuropathol (Berl) 1991; 81: 588-90.
19. Frackowiak J, Wisniewski HM, Wegiel J, Merz GS, Iqbal K, Wang KC. Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils. Acta Neuropathol 1992; 84: 225-33.
20. Banati RB, Gehrmann J, Czech C, Monning U, Jones LL, Konig G, Beyreuther K, Kreutzberg GW. Early and rapid de novo synthesis of Alzheimer beta A4-amyloid precursor protein (APP) in activated microglia. Glia 1993; 9: 199-210.
21. Ard MD, Cole GM, Wei J, Mehrle AP, Fratkin JD. Scavenging of Alzheimer's amyloid beta-protein by microglia in culture. J Neurosci Res 1996; 43: 190-202.
22. Paresce DM, Chung H, Maxfield FR. Slow degradation of aggregates of the Alzheimer's disease amyloid beta-protein by microglial cells. J Biol Chem 1997; 272: 29390-7.
23. Edison P, Archer HA, Hinz R, Hammers A, Pavese N, Tai YF, Hotton G, Cutler D, Fox N, Kennedy A, Rossor M, Brooks DJ. Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology 2007; 68: 501-8.
24. Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE, Hammers A, Tai YF, Fox N, Kennedy A, Rossor M, Brooks DJ. Microglia, amyloid, and cognition in Alzheimer's disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis 2008; 32: 412-19.
25. 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. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999; 400: 173-7.
26. 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. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 2000; 6: 916-19.
27. Wilcock DM, Gordon MN, Ugen KE, Gottschall PE, DiCarlo G, Dickey C, Boyett KW, Jantzen PT, Connor KE, Melachrino J, Hardy J, Morgan D. Number of Abeta inoculations in APP+PS1 transgenic mice influences antibody titers, microglial activation, and congophilic plaque levels. DNA Cell Biol 2001; 20: 731-6.
28. Wilcock DM, DiCarlo G, Henderson D, Jackson J, Clarke K, Ugen KE, Gordon MN, Morgan D. Intracranially administered anti-Abeta antibodies reduce beta-amyloid deposition by mechanisms both independent of and associated with microglial activation. J Neurosci 2003; 23: 3745-51.
29. Wilcock DM, Munireddy SK, Rosenthal A, Ugen KE, Gordon MN, Morgan D. Microglial activation facilitates Abeta plaque removal following intracranial anti-Abeta antibody administration. Neurobiol Dis 2004; 15: 11-20.
30. Janus C, Pearson J, McLaurin J, Mathews PM, Jiang Y, Schmidt SD, Chishti MA, Horne P, Heslin D, French J, Mount HT, Nixon RA, Mercken M, Bergeron C, Fraser PE, St George-Hyslop P, Westaway D. Abeta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 2000; 408: 979-82.
31. Morgan D, Diamond DM, Gottschall PE, Ugen KE, Dickey C, Hardy J, Duff K, Jantzen P, DiCarlo G, Wilcock D, Connor K, Hatcher J, Hope C, Gordon M, Arendash GW. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 2000; 408: 982-5.
32. Dodart JC, Bales KR, Gannon KS, Greene SJ, DeMattos RB, Mathis C, DeLong CA, Wu S, Wu X, Holtzman DM, Paul SM. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Nat Neurosci 2002; 5: 452-7.
33. Bard F, Barbour R, Cannon C, Carretto R, Fox M, Games D, Guido T, Hoenow K, Hu K, Johnson-Wood K, Khan K, Kholodenko D, Lee C, Lee M, Motter R, Nguyen M, Reed A, Schenk D, Tang P, Vasquez N, Seubert P, Yednock T. Epitope and isotype specificities of antibodies to beta -amyloid peptide for protection against Alzheimer's disease-like neuropathology. Proc Natl Acad Sci U S A 2003; 100: 2023-8.
34. Wilcock DM, Rojiani A, Rosenthal A, Levkowitz G, Subbarao S, Alamed J, Wilson D, Wilson N, Freeman MJ, Gordon MN, Morgan D. Passive amyloid immunotherapy clears amyloid and transiently activates microglia in a transgenic mouse model of amyloid deposition. J Neurosci 2004; 24: 6144-51.
35. Bayer AJ, Bullock R, Jones RW, Wilkinson D, Paterson KR, Jenkins L, Millais SB, Donoghue S. Evaluation of the safety and immunogenicity of synthetic Abeta42 (AN1792) in patients with AD. Neurology 2005; 64: 94-101.
36. Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 2003; 9: 448-52.
37. Ferrer I, Boada Rovira M, Sanchez Guerra ML, Rey MJ, Costa-Jussa F. Neuropathology and pathogenesis of encephalitis following amyloid-beta immunization in Alzheimer's disease. Brain Pathol 2004; 14: 11-20.
38. Nicoll JA, Barton E, Boche D, Neal JW, Ferrer I, Thompson P, Vlachouli C, Wilkinson D, Bayer A, Games D, Seubert P, Schenk D, Holmes C. Abeta species removal after Abeta42 immunization. J Neuropathol Exp Neurol 2006; 65: 1040-8.
39. Masliah E, Hansen L, Adame A, Crews L, Bard F, Lee C, Seubert P, Games D, Kirby L, Schenk D. Abeta vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease. Neurology 2005; 64: 129-31.
40. Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JAR. Long term effect of Abeta42 immunization in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 2008; 372: 216-23.
41. Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S, Michel BF, Boada M, Frank A, Hock C. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 2003; 61: 46-54.
42. Boche D, Barton E, Neal J, Ferrer I, Wilkinson D, Bayer A, Holmes C, Weller RO, Nicoll JAR. Effects of Aβ immunotherapy on cerebral amyloid angiopathy in human Alzheimer's disease. In British Neuropathological Society - 107th Meeting (Abstract). 107th Meeting of the British Neuropathological Society, Jan 11-13, 2006, London, England. Neuropathol Appl Neurobiol 2006; 32 (2): 223-4.
43. Boche D, Zotova E, Weller RO, Love S, Neal JW, Pickering RM, Wilkinson D, Holmes C, Nicoll JA. Consequence of Abeta immunization on the vasculature of human Alzheimer's disease brain. Brain 2008; 131: 3299-310.
44. Johnson-Wood K, Lee M, Motter R, Hu K, Gordon G, Barbour R, Khan K, Gordon M, Tan H, Games D, Lieberburg I, Schenk D, Seubert P, McConlogue L. Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci U S A 1997; 94: 1550-5.
45. Rabinowitz SS, Gordon S. Macrosialin, a macrophage-restricted membrane sialoprotein differentially glycosylated in response to inflammatory stimuli. J Exp Med 1991; 174: 827-36.
46. Rabinowitz S, Gordon S. Differential expression of membrane sialoglycoproteins in exudate and resident mouse peritoneal macrophages. J Cell Sci 1989; 93 (Pt 4): 623-30.
47. Neumann H, Kotter MR, Franklin RJ. Debris clearance by microglia: an essential link between degeneration and regeneration. Brain 2009; 132: 288-95.
48. Gehrmann J, Banati RB, Kreutzberg GW. Microglia in the immune surveillance of the brain: human microglia constitutively express HLA-DR molecules. J Neuroimmunol 1993; 48: 189-98.
49. DiPatre PL, Gelman BB. Microglial cell activation in aging and Alzheimer disease: partial linkage with neurofibrillary tangle burden in the hippocampus. J Neuropathol Exp Neurol 1997; 56: 143-9.
50. Streit WJ, Sparks DL. Activation of microglia in the brains of humans with heart disease and hypercholesterolemic rabbits. J Mol Med 1997; 75: 130-8.
51. Perlmutter LS, Scott SA, Barron E, Chui HC. MHC class II-positive microglia in human brain: association with Alzheimer lesions. J Neurosci Res 1992; 33: 549-58.
52. Gordon MN, Holcomb LA, Jantzen PT, DiCarlo G, Wilcock D, Boyett KW, Connor K, Melachrino J, O'Callaghan JP, Morgan D. Time course of the development of Alzheimer-like pathology in the doubly transgenic PS1+APP mouse. Exp Neurol 2002; 173: 183-95.
53. Perry VH, Nicoll JA, Holmes C. Microglia in neurodegenerative disease. Nat Rev Neurol 2010; 6: 193-201.
54. Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 2009; 27: 119-45.
55. Perry VH, Cunningham C, Holmes C. Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 2007; 7: 161-7.