PL EN


Preferences help
enabled [disable] Abstract
Number of results
2006 | 6 | 2 | 108-115
Article title

Immunologiczne aspekty choroby Alzheimera

Content
Title variants
EN
Immunological aspects of Alzheimer’s disease
Languages of publication
EN PL
Abstracts
EN
Alzheimer’s disease (AD) is an incurable neurodegenerative disease, which is accompanied by chronic inflammation. The immune system has an important role in the process of the disease. The deposition of amyloid β (Aβ) protein is a key pathological feature in Alzheimer’s disease. This article reviews immunotherapeutic strategies against AD. In murine models of AD, both active and passive immunization against Aβ induces a marked reduction in an amyloid brain burden and an improvement in cognitive functions. The findings from murine studies lead to clinical studies. One Phase II clinical trial of active immunization against Aβ was discontinued after 18 patients developed meningoencephalitis. After this lesson learned, new immunotherapeutic strategies, including both active and passive immunization, are investigated in clinical centers.
PL
Choroba Alzheimera (AD) jest nieuleczalną chorobą neurodegeneracyjną, której towarzyszy przewlekły proces zapalny. Układ immunologiczny może mieć istotny wpływ na przebieg procesu chorobowego. Głównym patologicznym wyznacznikiem choroby Alzheimera jest gromadzenie w obrębie mózgu złogów β-amyloidu. W obecnym artykule przedstawiono informacje na temat możliwości zastosowania immunoterapii w leczeniu choroby Alzheimera. Metody immunoterapeutyczne, mające usuwać amyloid β z chorych mózgów, dały bardzo pozytywne rezultaty w badaniach na zwierzętach. Zarówno metody aktywnej, jak i biernej immunizacji powodowały wyraźne zmniejszenie zawartości amyloidu w mózgach myszy transgenicznych oraz poprawę ich funkcji poznawczych. Bardzo dobre wyniki na modelach zwierzęcych pozwoliły przeprowadzić wstępne badania kliniczne. Ich wyniki są również obiecujące, choć obarczone ryzykiem zapalenia mózgu. Jedyne dotychczas badanie II Fazy z zastosowaniem szczepionki przeciwko Aβ zostało przerwane z powodu rozwoju u 18 pacjentów zapalenia opon mózgowych i mózgu. Obecnie ośrodkach badawczych pojawiają się nowe rodzaje technik immunoterapeutycznych.
Discipline
Year
Volume
6
Issue
2
Pages
108-115
Physical description
References
  • 1. Hardy J., Selkoe D.J.: The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002; 297: 353-356.
  • 2. Braak H., Braak E.: Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. (Berl.) 1991; 82 (4): 239-259.
  • 3. Games D., Adams D., Alessandrini R. i wsp.: Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 1995; 373: 523-527.
  • 4. Oddo S., Caccamo A., Shepherd J.D. i wsp.: Tripletransgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 2003; 39: 409-421.
  • 5. Hsia A.Y., Masliah E., McConlogue L. i wsp.: Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models. Proc. Natl Acad. Sci. U.S.A. 1999; 96: 3228-3233.
  • 6. Gouras G.K., Tsai J., Naslund J. i wsp.: Intraneuronal Abeta42 accumulation in human brain. Am. J. Pathol. 2000; 156: 15-20.
  • 7. Chen G., Chen K.S., Knox J. i wsp.: A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer’s disease. Nature 2000; 408: 975-979.
  • 8. Oddo S., Billings L., Kesslak J.P. i wsp.: Abeta immunotherapy leads to clearance of early, but not late, hyper-phosphorylated tau aggregates via the proteasome. Neuron 2004; 43: 321-332.
  • 9. Haga S., Akai K., Ishii T.: Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody. Acta Neuropathol. (Berl.) 1989; 77: 569-575.
  • 10. Rogers J., Cooper N.R., Webster S. i wsp.: Complement activation by beta-amyloid in Alzheimer disease. Proc. Natl Acad. Sci. U.SA 1992; 1; 89: 10016-10020.
  • 11. Meda L., Cassatella M.A., Szendrei G.I. i wsp.: Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature 1995; 13; 374: 647-650.
  • 12. Akiyama H., Barger S., Barnum S. i wsp.: Inflammation and Alzheimer’s disease. Neurobiol. Aging 2000; 21: 383-421.
  • 13. Mackenzie I.R., Munoz D.G.: Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology 1998, Apr. 50 (4): 986-990.
  • 14. D’Andrea M.R., Reiser P.A., Polkovitch D.A. i wsp.: The use of formic acid to embellish amyloid plaque detection in Alzheimer’s disease tissues misguides key observations. Neurosci. Lett. 2003; 342 (2): 114-118.
  • 15. McGeer P.L., Klegeris A., Walker D.G. i wsp.: Pathological proteins in senile plaques. Tohoku J. Exp. Med. 1994; 174: 269-277.
  • 16. Van Groen T., Liu L., Ikonen S., Kadish I.: Diffuse amyloid deposition, but not plaque number, is reduced in amyloid precursor protein/presenilin 1 double-transgenic mice by pathway lesions. Neuroscience 2003; 119: 1185-1197.
  • 17. Shaffer L.M., Dority M.D., Gupta-Bansal R. i wsp.: Amyloid β protein ^β) removal by neuroglial cells in culture. Neurobiol. Aging 1995; 16 (5): 737-745.
  • 18. Lemere C.A., Blusztajn J.K., Yamaguchi H. i wsp.: Sequence of deposition of heterogeneous amyloid beta-peptides and Apo E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol. Dis. 1996; 3: 26-32.
  • 19. Motte J., Williams R.S.: Age-related changes in the density and morphology of plaques and neurofibrillary tangles in Down syndrome brain. Acta Neuropathol. 1989; 77: 535-546.
  • 20. Wojtera M., Sikorska B., Sobow T., Liberski P.P.: Microglial cells in neurodegenerative disorders. Folia Neuropathol. 2005; 43: 311-321 (review).
  • 21. Meda L., Baron P., Scarlato G.: Glial activation in Alzheimer’s disease: the role of Abeta and its associated proteins. Neurobiol. Aging 2001; 22: 885-893.
  • 22. Honda S., Sasaki Y., Ohsawa K. i wsp.: Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi...o-coupled P2Y receptors. J. Neurosci. 2001; 21: 1975-1982.
  • 23. Shen Y., Li R., McGeer E.G., McGeer P.L.: Neuronal expression of mRNAs for complement proteins of the classical pathway in Alzheimer brain. Brain Res. 1997; 769: 391-395.
  • 24. Paresce D.M., Ghosh R.N., Maxfield F.R.: Microglial cells internalize aggregates of the Alzheimer’s disease amyloid beta-protein via a scavenger receptor. Neuron 1996; 17: 553-565.
  • 25. Wyss-Coray T, McConlogue L., Kindy M. i wsp.: Key signaling pathways regulate the biological activities and accumulation of amyloid-β. Neurobiol. Aging 2001; 22: 967-973.
  • 26. Yazawa H., Yu Z.X., Takeda, Le Y. i wsp.: Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages. FASEB J. 2001; 15: 2454-2462.
  • 27. Weggen S., Eriksen J.L., Das P. iwsp.: Asubset of NSAIDs lower amyloidogenic AB42 independently of cyclooxygenase activity. Nature 2001; 414: 212-216.
  • 28. Takahashi Y., Hayashil., Tominari Y. iwsp.: Sulindac sulfide is a noncompetitive γ-secretase inhibitor that preferentially reduces Λβ42 generation. J. Biol. Chem. 2003; 278: 18664-18670.
  • 29. Marambaud P., Ancolio K., Lopez-Perez E., Checler F.: Proteasome inhibitors prevent the degradation of familial Alzheimer’s disease-linked presenilin 1 and potentiate Λβ42 recovery from human cells. Mol. Med. 1998; 4: 147-157.
  • 30. Jantzen PT., Connor K.E., DiCarlo G. i wsp.: Microglial activation and beta -amyloid deposit reduction caused by a nitric oxide-releasing nonsteroidal anti-inflammatory drug in amyloid precursor protein plus presenilin-1 transgenic mice. J. Neurosci. 2002 Mar 15; 22 (6): 2246-2254.
  • 31. Myriad. Molecule of the month. MPC-7869 (Flurizan). Drug News Perspect. 2005; 18: 141.
  • 32. Xu S., Gaskin F.: Increased incidence of antibeta-amyloid autoantibodies secreted by Epstein - Barr virus transformed B cell lines from patients with Alzheimer’s disease. Mech. Ageing Dev. 1997; 94: 213-222.
  • 33. Hyman B.T.. Smith C., Buldyrev I. i wsp.: Autoantibodies to amyloidbeta and Alzheimer’s disease. Ann. Neurol. 2001: 49: 808-810.
  • 34. Brettschneider S., Morgenthaler N.G., Teipel S.J. i wsp.: Decreased serum amyloid beta (1-42) autoantibody levels in Alzheimer’s disease, determined by a newly developed immunoprecipitation assay with radiolabeled amyloid beta (1-42) peptide. Biol. Psychiatry 2005, Apr 1; 57 (7): 813-816.
  • 35. Weksler M.E., Gouras G., Relkin N.R., Szabo P.: The immune system, amyloid-b peptide, and Alzheimer’s disease. Immunological Reviews 2005; 205: 244-256.
  • 36. Weksler M.E., Relkin N., Turkenich R. i wsp.: Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals. Exp. Gerontol. 2002; 37: 943-948.
  • 37. Trieb K., Ransmayr G., Sgonc R. i wsp.: APP peptides stimulate lymphocyte proliferation in normals, but not in patients with Alzheimer’s disease. Neurobiol. Aging 1996; 17: 541-547; 2002; 298: 137.
  • 38. Monsonego A., Maron R., Zota V i wsp.: Immune hypore-sponsiveness to amyloid beta-peptide in amyloid precursor protein transgenic mice: implications for the pathogenesis and treatment of Alzheimer’s disease. Proc. Natl Acad. Sci. U.SA 2001; 98: 10273-10278.
  • 39. Monsonego A., Weiner H.L.: Immunotherapeutic approaches to Alzheimer’s disease. Science 2003; 302: 834-838.
  • 40. Weiner H.L., Selkoe D.J.: Inflammation and therapeutic vaccination in CNS diseases. Nature 2002; 420: 879-884.
  • 41. Solomon B., Koppel R., Frenkel D., Hanan-Aharon E.: Disaggregation of Alzheimer β-amyloid by site-directed mAb. Proc. Natl Acad. Sci. U.S.A. 1997; 94: 4109-4112.
  • 42. Janus C., Pearson J., McLaurin J. iwsp.: Aβpeptide immunization reduces behavioural impairment and plaques in a model of Alzheimer’s disease. Nature 2000; 408: 979-982.
  • 43. Schenk D., Barbour R., Dunn W i wsp.: Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999; 400: 173-177.
  • 44. Weiner H.L., Lemere C.A., Maron R. i wsp.: Nasal administration of amyloid-β peptide decreases cerebral amyloid burden in a mouse model of Alzheimer’s disease. Ann. Neurol. 2000; 48: 567-579.
  • 45. Frenkel D., Balass M., Solomon B.: N-terminal EFRH sequence of Alzheimer’s β-amyloid peptide represents the epitope of its anti-aggregating antibodies. J. Neuroimmunol. 1998; 88: 85-90.
  • 46. Sigurdsson E.M., Scholtzova H., Mehta PD. i wsp.: Immunization with a nontoxic/nonfibrillar amyloid-β homologous peptide reduces Alzheimer’s disease-associated pathology in transgenic mice. Am. J. Pathol. 2001; 159: 439-447.
  • 47. Frenkel D., Katz O., Solomon B.: Immunization against Alzheimer’s β-amyloid plaques via EFRH phage administration. Proc. Natl Acad. Sci. U.S.A. 2000; 97:11455-11459.
  • 48. Frenkel D., Maron R., Burt D.S., Weiner H.L.: Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears β-amyloid in a mouse model of Alzheimer disease. J. Clin. Invest. 2005; 115: 2423-2433.
  • 49. DeMattos R.B., Bales K.R. i wsp.: Peripheral anti^ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer’s disease. Proc. Natl Acad. Sci. U.S.A. 2001; 98: 8850-8855.
  • 50. Lee E.B., Leng L.Z., Zhang B. i wsp.: Targeting Aβ oligomers by passive immunization with a conformation selective monoclonal antibody improves learning and memory in APP transgenic mice. J. Biol. Chem. 2005; 281: 4292-4299.
  • 51. Klyubin I., Walsh D.M., Lemere C.A. i wsp.: Amyloid β protein immunotherapy neutralizes Aβ oligomers that disrupt synaptic plasticity in vivo. Nature Med. 2005; 11: 556-561.
  • 52. Wilcock D.M., Munireddy S.K., Rosenthal A. i wsp.: Microglial activation facilitates Aβ plaque removal following intracranial anti-Aβ antibody administration. Neuro-biol. Dis. 2004; 15: 11-20.
  • 53. Pfeifer M., Boncristiano S., Bondolfi L. i wsp.: Cerebral hemorrhage after passive anti^ immunotherapy. Science 2002; 298: 1379.
  • 54. Racke M.M., Boone L.I., Hepburn D.L. i wsp.: Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid β. J. Neurosci. 2005; 25: 629-636.
  • 55. Bayer A.J., Bullock R., Jones RW iwsp.: Evaluation of the safety and immunogenicity of synthetic Aβ42 (AN1792) in patients with AD. Neurology 2005; 64: 94-101.
  • 56. Orgogozo J.M., Gilman S., Dartigues J.F. i wsp.: Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization. Neurology 2003; 61: 46-54.
  • 57. Gilman S., Koller M., Black R.S. i wsp.: Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005; 64: 1553-1562.
  • 58. Hock C., Konietzko U., Streffer J.R. i wsp.: Antibodies against β-amyloid slow cognitive decline in Alzheimer’s disease. Neuron 2003; 38: 547-554.
  • 59. Ferrer I., Boada Rovira i wsp.: Neuropathology and pathogenesis of encephalitis following amyloid-β immunization in Alzheimer’s disease. Brain Pathol. 2004; 14: 11-20.
  • 60. Nicoll J.A., Wilkinson D., Holmes C. i wsp.: Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report. Nature Med. 2003; 9: 448-452.
  • 61. Masliah E., Hansen L., Adame A. i wsp.: Aβ vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease. Neurology 2005; 64: 129-131.
  • 62. Monsonego A., ZotaV, Karni A. iwsp.: Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. J. Clin. Invest. 2003; 112: 415-422.
  • 63. O’Toole M., Janszen D.B., Slonim D.K. i wsp.: Risk factors associated with β-amyloid1-42 immunotherapy in preimmunization gene expression patterns of blood cells. Arch. Neurol. 2005; 62: 1531-1536.
  • 64. Schenk D., Hagen M., Seubert P: Current progress in β-amyloid immunotherapy. Curr. Opin. Immunol. 2004; 16: 599-606.
Document Type
article
Publication order reference
YADDA identifier
bwmeta1.element.psjd-4ac4a2e0-d88e-48db-ba5b-b24e54f62e3d
Identifiers
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.