Neurobiology of Aging
Volume 31, Issue 5 , Pages 747-757 , May 2010

Inflammatory changes are tightly associated with neurodegeneration in the brain and spinal cord of the APP/PS1KI mouse model of Alzheimer's disease

  • Oliver Wirths

      Affiliations

    • Division of Molecular Psychiatry and Alzheimer Ph.D. Graduate School, Department of Psychiatry, University of Goettingen, von-Siebold-Str. 5, 37075 Goettingen, Germany
    • Corresponding Author InformationCorresponding author at: Department of Psychiatry, Division of Molecular Psychiatry, University of Göttingen, Von-Siebold-Strasse 5, 37075 Göttingen, Germany. Tel.: +49 551 39 10290; fax: +49 551 39 10291.
  • ,
  • Henning Breyhan

      Affiliations

    • Division of Molecular Psychiatry and Alzheimer Ph.D. Graduate School, Department of Psychiatry, University of Goettingen, von-Siebold-Str. 5, 37075 Goettingen, Germany
  • ,
  • Andrea Marcello

      Affiliations

    • Division of Molecular Psychiatry and Alzheimer Ph.D. Graduate School, Department of Psychiatry, University of Goettingen, von-Siebold-Str. 5, 37075 Goettingen, Germany
  • ,
  • Marie-Caroline Cotel

      Affiliations

    • Division of Molecular Psychiatry and Alzheimer Ph.D. Graduate School, Department of Psychiatry, University of Goettingen, von-Siebold-Str. 5, 37075 Goettingen, Germany
  • ,
  • Wolfgang Brück

      Affiliations

    • University of Goettingen, Department of Neuropathology, Robert-Koch-Str. 40, 37075 Göttingen, Germany
  • ,
  • Thomas A. Bayer

      Affiliations

    • Division of Molecular Psychiatry and Alzheimer Ph.D. Graduate School, Department of Psychiatry, University of Goettingen, von-Siebold-Str. 5, 37075 Goettingen, Germany

Received 31 January 2008 ,Revised 20 June 2008 ,Accepted 20 June 2008.

References 

  1. Ahn YH, Lee G, Kang SK. Molecular insights of the injured lesions of rat spinal cords: inflammation, apoptosis, and cell survival. Biochem. Biophys. Res. Commun. 2006;348(2):560–570
  2. Apelt J, Schliebs R. Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Res. 2001;894(1):21–30
  3. Bechmann I, Goldmann J, Kovac AD, Kwidzinski E, Simburger E, Naftolin F, et al. Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia. FASEB J. 2005;19(6):647–649
  4. Benzing WC, Wujek JR, Ward EK, Shaffer D, Ashe KH, Younkin SG, et al. Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice. Neurobiol. Aging. 1999;20(6):581–589
  5. Boom A, Pochet R, Authelet M, Pradier L, Borghgraef P, Van Leuven F, et al. Astrocytic calcium/zinc binding protein S100A6 over expression in Alzheimer's disease and in PS1/APP transgenic mice models. Biochim. Biophys. Acta. 2004;1742(1–3):161–168
  6. Bornemann KD, Wiederhold KH, Pauli C, Ermini F, Stalder M, Schnell L, et al. Abeta-induced inflammatory processes in microglia cells of APP23 transgenic mice. Am. J. Pathol. 2001;158(1):63–73
  7. Carrasco J, Adlard P, Cotman C, Quintana A, Penkowa M, Xu F, et al. Metallothionein-I and -III expression in animal models of Alzheimer disease. Neuroscience. 2006;143(4):911–922
  8. Casas C, Sergeant N, Itier JM, Blanchard V, Wirths O, van der Kolk N, et al. Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42 accumulation in a novel Alzheimer transgenic model. Am. J. Pathol. 2004;165(4):1289–1300
  9. Chen K, Iribarren P, Hu J, Chen J, Gong W, Cho EH, et al. Activation of Toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid beta peptide. J. Biol. Chem. 2006;281(6):3651–3659
  10. Dickson DW. The pathogenesis of senile plaques. J. Neuropathol. Exp. Neurol. 1997;56(4):321–339
  11. Eikelenboom P, Veerhuis R, Scheper W, Rozemuller AJ, van Gool WA, Hoozemans JJ. The significance of neuroinflammation in understanding Alzheimer's disease. J. Neural. Transm. 2006;113(11):1685–1695
  12. Frautschy SA, Yang F, Irrizarry M, Hyman B, Saido TC, Hsiao K, et al. Microglial response to amyloid plaques in APPsw transgenic mice. Am. J. Pathol. 1998;152(1):307–317
  13. German DC, Liang CL, Song T, Yazdani U, Xie C, Dietschy JM. Neurodegeneration in the Niemann–Pick C mouse: glial involvement. Neuroscience. 2002;109(3):437–450
  14. Gordon MN, Holcomb LA, Jantzen PT, DiCarlo G, Wilcock D, Boyett KW, et al. Time course of the development of Alzheimer-like pathology in the doubly transgenic PS1+APP mouse. Exp. Neurol. 2002;173(2):183–195
  15. Griffin WS, Sheng JG, Roberts GW, Mrak RE. Interleukin-1 expression in different plaque types in Alzheimer's disease: significance in plaque evolution. J. Neuropathol. Exp. Neurol. 1995;54(2):276–281
  16. Hashimoto M, Sun D, Rittling SR, Denhardt DT, Young W. Osteopontin-deficient mice exhibit less inflammation, greater tissue damage, and impaired locomotor recovery from spinal cord injury compared with wild-type controls. J. Neurosci. 2007;27(13):3603–3611
  17. Heneka MT, Sastre M, Dumitrescu-Ozimek L, Dewachter I, Walter J, Klockgether T, et al. Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice. J. Neuroinflamm. 2005;2:22
  18. Herber DL, Mercer M, Roth LM, Symmonds K, Maloney J, Wilson N, et al. Microglial activation is required for Abeta clearance after intracranial injection of lipopolysaccharide in APP transgenic mice. J. Neuroimmune Pharmacol. 2007;2(2):222–231
  19. Hidalgo J, Penkowa M, Espejo C, Martinez-Caceres EM, Carrasco J, Quintana A, et al. Expression of metallothionein-I, -II, and -III in Alzheimer disease and animal models of neuroinflammation. Exp. Biol. Med. (Maywood). 2006;231(9):1450–1458
  20. Hoyaux D, Alao J, Fuchs J, Kiss R, Keller B, Heizmann CW, et al. S100A6, a calcium- and zinc-binding protein, is overexpressed in SOD1 mutant mice, a model for amyotrophic lateral sclerosis. Biochim. Biophys. Acta. 2000;1498(2–3):264–272
  21. Kim S, Ock J, Kim AK, Lee HW, Cho JY, Kim DR, et al. Neurotoxicity of microglial cathepsin D revealed by secretome analysis. J. Neurochem. 2007;
  22. Kohler C, Ebert U, Baumann K, Schroder H. Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels. Neurobiol. Dis. 2005;20(2):528–540
  23. Letiembre M, Liu Y, Walter S, Hao W, Pfander T, Wrede A, et al. Screening of innate immune receptors in neurodegenerative diseases: a similar pattern. Neurobiol. Aging. 2007;
  24. Maslinska D, Laure-Kamionowska M, Maslinski KT, Gujski M, Maslinski S. Distribution of tryptase-containing mast cells and metallothionein reactive astrocytes in human brains with amyloid deposits. Inflamm. Res. 2007;56(Suppl. 1):S17–S18
  25. 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(8):1285–1291
  26. Mehlhorn G, Hollborn M, Schliebs R. Induction of cytokines in glial cells surrounding cortical beta-amyloid plaques in transgenic Tg2576 mice with Alzheimer pathology. Int. J. Dev. Neurosci. 2000;18(4–5):423–431
  27. Myerowitz R, Lawson D, Mizukami H, Mi Y, Tifft CJ, Proia RL. Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling. Hum. Mol. Genet. 2002;11(11):1343–1350
  28. Olson JK, Miller SD. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J. Immunol. 2004;173(6):3916–3924
  29. Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic. Acids Res. 2002;30(9):e36
  30. Pihlaja R, Koistinaho J, Malm T, Sikkila H, Vainio S, Koistinaho M. Transplanted astrocytes internalize deposited beta-amyloid peptides in a transgenic mouse model of Alzheimer's disease. Glia. 2007;
  31. Qiao X, Cummins DJ, Paul SM. Neuroinflammation-induced acceleration of amyloid deposition in the APPV717F transgenic mouse. Eur. J. Neurosci. 2001;14(3):474–482
  32. Richards JG, Higgins GA, Ouagazzal AM, Ozmen L, Kew JN, Bohrmann B, et al. PS2APP transgenic mice, coexpressing hPS2mut and hAPPswe, show age-related cognitive deficits associated with discrete brain amyloid deposition and inflammation. J. Neurosci. 2003;23(26):8989–9003
  33. 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(4):339–349
  34. Scatena M, Liaw L, Giachelli CM. Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler. Thromb. Vasc. Biol. 2007;27(11):2302–2309
  35. Stalder M, Phinney A, Probst A, Sommer B, Staufenbiel M, Jucker M. Association of microglia with amyloid plaques in brains of APP23 transgenic mice. Am. J. Pathol. 1999;154(6):1673–1684
  36. Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, et al. Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science. 2005;307(5713):1282–1288
  37. Tahara K, Kim HD, Jin JJ, Maxwell JA, Li L, Fukuchi K. Role of toll-like receptor signalling in Abeta uptake and clearance. Brain. 2006;129(Pt 11):3006–3019
  38. Udan ML, Ajit D, Crouse NR, Nichols MR. Toll-like receptors 2 and 4 mediate Abeta(1-42) activation of the innate immune response in a human monocytic cell line. J. Neurochem. 2008;104(2):524–533
  39. Vasto S, Mocchegiani E, Malavolta M, Cuppari I, Listi F, Nuzzo D, et al. Zinc and inflammatory/immune response in aging. Ann. N.Y. Acad. Sci. 2007;1100:111–122
  40. Walter S, Letiembre M, Liu Y, Heine H, Penke B, Hao W, et al. Role of the toll-like receptor 4 in neuroinflammation in Alzheimer's disease. Cell Physiol. Biochem. 2007;20(6):947–956
  41. Wang D, Ayers MM, Catmull DV, Hazelwood LJ, Bernard CC, Orian JM. Astrocyte-associated axonal damage in pre-onset stages of experimental autoimmune encephalomyelitis. Glia. 2005;51(3):235–240
  42. Wirths O, Breyhan H, Schafer S, Roth C, Bayer TA. Deficits in working memory and motor performance in the APP/PS1ki mouse model for Alzheimer's disease. Neurobiol. Aging. 2008;29(6):891–901
  43. Wirths O, Multhaup G, Czech C, Feldmann N, Blanchard V, Tremp G, et al. Intraneuronal APP/A beta trafficking and plaque formation in beta-amyloid precursor protein and presenilin-1 transgenic mice. Brain Pathol. 2002;12(3):275–286
  44. Wirths O, Weis J, Kayed R, Saido TC, Bayer TA. Age-dependent axonal degeneration in an Alzheimer mouse model. Neurobiol. Aging. 2007;28(11):1689–1699
  45. Wirths O, Weis J, Szczygielski J, Multhaup G, Bayer TA. Axonopathy in an APP/PS1 transgenic mouse model of Alzheimer's disease. Acta Neuropathol. 2006;111(4):312–319
  46. Wyss-Coray T, Lin C, Yan F, Yu GQ, Rohde M, McConlogue L, et al. TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nat. Med. 2001;7(5):612–618

PII: S0197-4580(08)00218-2

doi: 10.1016/j.neurobiolaging.2008.06.011

Neurobiology of Aging
Volume 31, Issue 5 , Pages 747-757 , May 2010