Skip to main content

Cognitive impairment in antiphospholipid syndrome: evidence from animal models

Abstract

Although antiphospholipid syndrome (APS) is a multisystem prothrombotic condition, its inflammatory nature has been increasingly recognized in recent years. Stroke and transitory ischemic attacks are the neurological manifestations included in APS criteria, however many other neurological involvements have been attributed to antiphospholipid antibodies (aPL), such as seizures, transverse myelitis, and cognitive impairment. In this article we will review evidence from animal model that explain the role of aPL in cognition.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. 1.

    Wilson WA, Gharavi AE, Koike T et al (1999) International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 42:1309–1311

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Miyakis S, Lockshin MD, Atsumi T, Branch DC, Brey RL, Cervera R et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemostasis 4:295–306

    Article  CAS  Google Scholar 

  3. 3.

    Chapman J, Rand JH, Brey RL, Levine SR, Blatt I, Khamashta MA, Shoenfeld Y (2003) Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies. Lupus 12:514–517

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Sanna G, Bertolaccini ML, Cuadrado MJ et al (2003) Central nervous system involvement in the antiphospholipid (Hughes) syndrome. Rheumatology 42:200–213

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Tomietto P, Annese V, D'agostini S, Venturini P, La Torre G, De Vita S, Ferraccioli GF (2007) General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus. Arthritis Rheum 57:1461–1472

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Mikdashi J, Handwerger B (2004) Predictors of neuropsychiatric damage in systemic lupus erythematosus: data from the Maryland lupus cohort. Rheumatology (Oxford) 43:1555–1560

    Article  CAS  Google Scholar 

  7. 7.

    McLaurin EY, Holliday SL, Williams P, Brey RL (2005) Predictors of cognitive dysfunction in patients with systemic lupus erythematosus. Neurology 64:297–303

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Tektonidou MG, Varsou N, Kotoulas G, Antoniou A, Moutsopouls HM (2006) Cognitive deficits in patients with antiphospholipid syndrome: association with clinical, laboratory, and brain magnetic resonance imaging finding. Arch Int Med 166:2278–2284

    Article  Google Scholar 

  9. 9.

    Aharon-Peretz J, Brenner B, Amyel E et al (1995) Neurocgnitive dysfunction in antiphospholipid antibody syndrome (APS). Lupus 4:101

    Google Scholar 

  10. 10.

    Erkan D, Kozora E, Lockshin MD (2011) Cognitive dysfunction and white matter abnormalities in antiphospholipid syndrome. Pathophysiology 18:93–102

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Chapman J, Abu-Katash M, Inzelberg R et al (2002) Prevalence and clinical features of dementia associated with the antiphospholipid syndrome and circulating anticoagulants. J Neurol Sci 203–204:81–84

    PubMed  Article  Google Scholar 

  12. 12.

    Levine SR, Welch KMA (1987) The spectrum of neurologic disease associated with antiphospholipid antibodies. Lupus anticoagulants and anticardiolipin antibodies. Arch Neurol 44:876–883

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Liberato B, Levy RA (2007) Antiphospholipid syndrome and cognition. Clin Rev Allergy Immunol 32:188–191

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Hess DC, Taormina M, Thompson J et al (1993) Cognitive and neurologic deficits in the MRL/lpr mouse: a clinicopathologic study. J Rheumatol 20:610–617

    PubMed  CAS  Google Scholar 

  15. 15.

    Ziporen L, Shoenfeld Y, Levy Y, Korczyn AD (1997) Neurological dysfunction and hyperactive behavior associated with antiphospholipid antibodies. A mouse model. J Clin Invest 100:613–9.10

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Shoenfeld Y, Nahum A, Korczyn AD et al (2003) Neuronal-binding antibodies from patients with antiphospholipid syndrome induce cognitive deficits following intrathecal passive transfer. Lupus 12:436–442

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Chapman J, Cohen-Armon M, Shoenfeld Y, Korczyn AD (1999) Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes. Lupus 8:127–133

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Cimaz R, Meroni PL, Shoenfeld Y (2006) Epilepsy as part of systemic lupus erythematosus and systemic antiphospholipidsyndrome (Hughe’s syndrome). Lupus 15:191–197

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Appenzeller S, Cendes F, Costallat LT (2004) Epileptic seizures in systemic lupus erythematosus. Neurology 63:1808–1812

    PubMed  Google Scholar 

  20. 20.

    Herranz MT, Rivier G, Khamashta MA, Blaser KU, Hughes GR (1994) Association between antiphospholipid antibodies and epilepsy in patients with systemic lupus erythematosus. Arthritis Rheum 37:568–571

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Katzav A, Litvinjuk Y, Pick CG et al (2006) Genetic and immunological factors interact in a mouse model of CNS antiphospholipid syndrome. Behav Brain Res 169:289–293

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Chapman J, Shoenfeld Y (2002) Neurological and neuroendocrine-cytokine inter-relationship in the antiphospholipid syndrome. Ann N Y Acad Sci 966:415–424

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Katzav A, Shrot S, Litvinjuk Y et al (2001) Cognitive and behavioral deficits develop late in a mouse model of the antiphospholipid syndrome (APS). Neurology 56:A472

    Google Scholar 

  24. 24.

    Shrot S, Katzav A, Korczyn AD et al (2002) Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies. Lupus 11:736–743

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Aron AL, Cuellar ML, Brey RL et al (1995) Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I. Clin Exp Immunol 101:78–81

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Katzav A, Shoenfeld Y, Chapman J (2010) The pathogenesis of neural injury in animal models of the antiphospholipid syndrome. Clin Rev Allergy Immunol 38:196–200

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Nowacki P, Ronin-Walknowska E, Ossowicka-Stepinska J (1998) Central nervous system involvement in pregnant rabbits with experimental model of antiphospholipid syndrome. Folia Neuropathol 36:38–44

    PubMed  CAS  Google Scholar 

  28. 28.

    Nowacki P, Ronin-Walknowska E, Ossowicka-Stepinska J (1999) Neuropathological changes within the brain of rabbits with experimental model of antiphospholipid syndrome in different time after immunization. Folia Neuropathol 37:269–272

    PubMed  CAS  Google Scholar 

  29. 29.

    Meroni PL, Raschi E, Testoni C (2002) Endothelium as a target for anti-phospholipid antibodies and for therapeutical intervention. Autoimmun Rev 1:55–60

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Pierangeli SS, Chen PP, Raschi E et al (2008) Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms. Semin Thromb Hemost 34:236–250

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Soltesz P, Der H, Veres K et al (2008) Immunological features of primary anti-phospholipid syndrome in connection with endothelial dysfunction. Rheumatology (Oxford) 47:1628–1634

    Article  CAS  Google Scholar 

Download references

Acknowledgment

Dr. Appenzeller woul like to thank Fundação Apoio À Pesquisa Estado São Paulo-Brasil (FAPESP 2008/02917-0 and 2009/06049-6) and Conselho Nacional Pesquisa Desenvolvimento-Brasil CNPq (300447/2009-4). Lapa would like to thank Fundação Amparo À Pesquisa Estado São Paulo-Brasil (2010/13639-1). Dr. de Carvalho has received grant support from the Federico Foundation and CNPq (300665/2009-1).

Disclosures

None.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Simone Appenzeller.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Appenzeller, S., Lapa, A.T., Guirau, C.R. et al. Cognitive impairment in antiphospholipid syndrome: evidence from animal models. Clin Rheumatol 31, 403–406 (2012). https://doi.org/10.1007/s10067-011-1922-z

Download citation

Keywords

  • Animal models
  • Antiphospholipid syndrome
  • Cognitive impairment