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Vorzeitige Immunalterung: ein pathogenetischer Faktor bei Alzheimer-Demenz?

Premature immunosenescence: a pathogenetic factor in Alzheimer’s disease?

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Zusammenfassung

Während für die seltenen familiären Formen der Alzheimer-Demenz (AD) mehrere spezifische Genmutationen identifiziert werden konnten, ist die Ätiologie der weit häufiger auftretenden sporadischen Form nicht endgültig aufgeklärt. Ausgehend von einer multifaktoriellen Pathogenese gilt steigendes Alter als einer der wichtigsten Risikofaktoren. Darüber hinaus lassen Beobachtungen zu lokalen und systemischen immunologischen Auffälligkeiten eine Beteiligung des Immunsystems an der Pathogenese der Erkrankung vermuten. Neben Befunden zum Einfluss entzündlicher Faktoren lassen sich Hinweise für eine Abschwächung bestimmter Immunantworten beobachten. Möglicherweise beeinträchtigen vorzeitige Alterungsvorgänge im Sinne einer „prämaturen Immunoseneszenz“ bei AD eine adäquate Immunantwort. Vor diesem Hintergrund erscheint die Entwicklung verschiedener immuntherapeutischer Verfahren Erfolg versprechend.

Summary

While the familial form of Alzheimer’s disease (AD) is known to be entirely inherited, the etiopathogenesis of the most common late-onset form of Alzheimer’s disease still remains unresolved. Among various factors, aging seems to be one of the most prominent risk factors. Moreover, a large body of evidence points to the contribution of immunological alterations in AD. The involvement of inflammatory factors in the etiopathology has been widely discussed. Moreover, an impairment of certain immune responses in AD has been observed. Presumably, premature immunosenescence may lead to inadequate immune reactions. Against this background, the development of different immunotherapeutic strategies seems to be a promising challenge for future research.

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Literatur

  1. Akiyama H, Barger S, Barnum S et al (2000) Inflammation and Alzheimer’s disease. Neuroinflammation working group. Neurobiol Aging 21:383–421

    Article  CAS  PubMed  Google Scholar 

  2. Antonaci S, Garofalo AR, Chicco C et al (1990) Senile dementia, Alzheimer type: a distinct entity in the immunosenescence? J Clin Lab Anal 4:16–21

    Article  CAS  PubMed  Google Scholar 

  3. Bamberger ME, Landreth GE (2001) Microglial interaction with beta-amyloid: implications for the pathogenesis of Alzheimer’s disease. Microsc Res Tech 54:59–70

    Article  CAS  PubMed  Google Scholar 

  4. Blasko I, Grubeck-Loebenstein B (2003) Role of the immune system in the pathogenesis, prevention and treatment of Alzheimer’s disease. Drugs Aging 20:101–113

    Article  CAS  PubMed  Google Scholar 

  5. Dean R, Bell RD, Sagare A, Zklokovic BV (2009) Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer’s disease. CNS Neurol Disord Drug Targets 8(1):16–30

    Article  Google Scholar 

  6. DeMattos RB, Bales KR, Cummins DJ et al (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 19:8850–8855

    Article  Google Scholar 

  7. De la Monte SM, Luong T, Neely TR et al (2000) Mitochondrial DNA damage as a mechanism of cell loss in Alzheimer disease. Lab Invest 80:1323–1335

    Article  Google Scholar 

  8. Du Y, Dodel R, Hampel H (2001) Reduced levels of amyloid beta-peptide antibody in Alzheimer disease. Neurology 57:801–805

    CAS  PubMed  Google Scholar 

  9. Effros RB (1998) Replicative senescence in the immune system: Impact of the Hayflick limit on T cell function in the elderly. Am J Hum Genet 62:1003–1007

    Article  CAS  PubMed  Google Scholar 

  10. Fiala M, Lin J, Ringman J et al (2005) Ineffective phagocytosis of amyloid-β by macrophages of Alzheimer’s disease patients. J Alzheimers Dis 7:221–232

    CAS  PubMed  Google Scholar 

  11. Franceschi C, Monti D, Scarfi MR et al (1992) Genomic instability and aging. Studies in centenarians (successful aging) and in patients with Down’s syndrome (accelerated aging). Ann N Y Acad Sci 663:4–16

    Article  CAS  PubMed  Google Scholar 

  12. Giunta B, Fernandez F, Nikolic WV et al (2008) Inflammaging as a prodrome to Alzheimer’s disease. J Neuroinflammation 11:51

    Article  Google Scholar 

  13. Grimmer T, Perneczky R, Kurz A (2008) Aktueller Stand der Immuntherapie bei Alzheimer-Krankheit. Nervenarzt 79:822–845

    Article  Google Scholar 

  14. Guayerbas N, Puerto M, Victor VM et al (2002) Leukocyte function and life span in a murine model of premature immunosenescence. Exp Gerontol 37:249–256

    Article  CAS  PubMed  Google Scholar 

  15. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science 297:353–356

    Article  CAS  PubMed  Google Scholar 

  16. Jenner E (1798) An inquiry into the causes and effects of the variolae vaccine, or cow-pox. In: The three original publications on vaccination against smallpox. Vol. XXXVIII, Part 4 (2001). Collier PF, Son Bartleby.com, The Harvard Classics, New York, pp 1909–1014

  17. Kalaria RN (1993) The immunopathology of Alzheimer’s disease and some related disorders. Brain Pathol 3:333–347

    Article  CAS  PubMed  Google Scholar 

  18. Lee M, Sparatore A, Del Soldato P et al (2009) Hydrogen sulfide-releasing NSAIDs attenuate neuroinflammation induced by microglial and astrocytic activation. Glia 18: Epub ahead of print

    Google Scholar 

  19. 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

    Article  CAS  PubMed  Google Scholar 

  20. McGeer PL, McGeer EG (2001) Inflammation, autotoxicity and Alzheimer’s disease. Neurobiol Aging 22:799–809

    Article  CAS  PubMed  Google Scholar 

  21. Nandy K (1977) Immune reactions in aging brain and senile dementia. In: Nandy K, Sherwin I (eds) The aging brain and senile dementia. Plenum, New York, pp 181–196

  22. Panossian LA, Porter VR, Valenzuela HF et al (2003) Telomere shortening in T cells correlates with Alzheimer disease status. Neurobiol Aging 24:77–84

    Article  CAS  PubMed  Google Scholar 

  23. Park E, Alberti J, Mehta P et al (2000) Partial impaired immune functions in peripheral blood leukocytes from aged men with Down’s syndrome. Clin Immunol 95:62–69

    Article  CAS  PubMed  Google Scholar 

  24. Popovic M, Caballero-Bleda M, Puelles L, Popovic N (1998) Importance of immunological and inflammatory processes in the pathogenesis and therapy of Alzheimer’s disease. Int J Neurosci 95:203–236

    Article  CAS  PubMed  Google Scholar 

  25. Richartz E, Klein R, Stransky E et al (2004) Autoantibody reactivity in serum and cerebrospinal fluid of patients with Alzheimer’s disease. Neurol Psychiat Brain Res 11:145–148

    Google Scholar 

  26. Richartz E, Batra A, Stransky E et al (2005) Diminished production of proinflammatory cytokines in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 19:184–188

    Article  CAS  PubMed  Google Scholar 

  27. Richartz E, Batra A, Stransky E et al (2007) Altered lymphoycyte distribution in Alzheimer’s disease. J Psychiatr Res 41:1–8

    Article  Google Scholar 

  28. Richartz-Salzburger E (2008) Psychoimmunologische Forschung bei Alzheimer-Demenz. Monographien aus dem Gesamtgebiete der Psychiatrie. Bd 114. Steinkopff, Darmstadt

  29. Schenk D, Barbour R, Dunn W et al (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173–177

    Article  CAS  PubMed  Google Scholar 

  30. Singh VK, Fudenberg HH, Brown FR (1986–1987) Immunologic dysfunction: Simultaneous study of Alzheimer’s and older Down’s patients. Mech Ageing Dev 37:257–264

    Article  PubMed  Google Scholar 

  31. Singh VK (1997) Neuroautoimmunity: Pathogenetic implications for Alzheimer’s disease. Gerontology 43:79–94

    Article  CAS  PubMed  Google Scholar 

  32. Solomon B (2007) Antibody-mediated immunotherapy for Alzheimer’s disease. Curr Opin Investig Drugs 8:519–524

    CAS  PubMed  Google Scholar 

  33. Streit WJ (2002) Microglia as neuroprotective, immunocompetent cells of the CNS. Glia 40:133–139

    Article  PubMed  Google Scholar 

  34. Tan ZS, Beiser AS, Vasan RS et al (2007) Inflammatory markers and the risk of Alzheimer disease: the framingham study. Neurology 68:1902–1908

    Article  CAS  PubMed  Google Scholar 

  35. Wekerle H, Linington C, Lassmann H, Meyermann R (1986) Cellular immune reactivity within the CNS. Trends Neurosci 9:271–277

    Article  Google Scholar 

  36. Zhang J, Kong Q, Zhang Z et al (2003) Telomere dysfunction of lymphocytes in patients with Alzheimer’s disease. Cogn Behav Neurol 16:170–176

    Article  PubMed  Google Scholar 

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  1. Universitätsklinik für Psychiatrie und Psychotherapie, Tübingen, Osianderstraße 24, 72076, Tübingen, Deutschland

    E. Richartz-Salzburger, E. Stransky, C. Laske & N. Köhler

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  1. E. Richartz-Salzburger
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  2. E. Stransky
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  3. C. Laske
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  4. N. Köhler
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Correspondence to E. Richartz-Salzburger.

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Richartz-Salzburger, E., Stransky, E., Laske, C. et al. Vorzeitige Immunalterung: ein pathogenetischer Faktor bei Alzheimer-Demenz?. Nervenarzt 81, 837–843 (2010). https://doi.org/10.1007/s00115-009-2918-7

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