Skip to main content

Advertisement

SpringerLink
Log in

Anti-MAG autoantibodies are increased in Parkinson’s disease but not in atypical parkinsonism

  • Neurology and Preclinical Neurological Studies - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

There is emerging evidence that glial cells are involved in the neuropathological process in Parkinson’s disease (PD) in addition to degeneration of neuronal structures. Recently, we confirmed the presence of an adaptive immune response against different glial-derived antigens in PD, with a possible role of anti-MAG, anti-MBP and anti-PLP antibodies in the disease progression. The aim of the present study was to assess humoral response against myelin-associated glycoprotein (MAG) in patients with parkinsonism (both idiopathic and atypical) to check whether these antibodies could serve as biomarkers of PD, its severity and progression. Anti-MAG autoantibodies were measured by an ELISA system in 99 PD patients, 33 atypical parkinsonism patients, and 36 control subjects. In PD patients, anti-MAG IgM autoantibodies were significantly higher in comparison to healthy control subjects (p = 0.038). IgM anti-MAG autoantibodies titers were also significantly higher in the whole group of patients with parkinsonism (either idiopathic or atypical) in comparison to healthy control subjects (1.88 ± 0.84 vs 1.70 ± 1.19, p = 0.017). This difference was mainly driven by the PD group, as the atypical parkinsonism group did not differ significantly from the control group in anti-MAG antibody levels (p = 0.51). A negative correlation between anti-MAG levels and disease duration was found in PD patients. Our study provides evidence for an increased production of autoantibodies against a protein of glial origin in PD. The negative correlation between anti-MAG antibodies and disease duration may suggest possible involvement of the immune system in disease progression. Increasing evidence that glia are involved in the neurodegenerative process to a greater extent than previously thought may turn out be useful in the search for biomarkers of the neurodegenerative process in PD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ahmed Z, Asi YT, Lees AJ et al (2013) Identification and quantification of oligodendrocyte precursor cells in multiple system atrophy, progressive supranuclear palsy and Parkinson’s disease. Brain Pathol 23:263–273

    Article  PubMed  Google Scholar 

  • Arima K (2006) Ultrastructural characteristics of tau filaments in tauopathies: immuno-electron microscopic demonstration of tau filaments in tauopathies. Neuropathology 26:475–483

    Article  PubMed  Google Scholar 

  • Besong-Agbo D, Wolf E, Jessen F et al (2013) Naturally occurring alpha-synuclein autoantibody levels are lower in patients with Parkinson disease. Neurology 80:169–175

    Article  CAS  PubMed  Google Scholar 

  • Burke RE, Dauer WT, Vonsattel JP (2008) A critical evaluation of the Braak staging scheme for Parkinson’s disease. Ann Neurol 64:485–491

    Article  PubMed  PubMed Central  Google Scholar 

  • Campbell BC, McLean CA, Culvenor JG et al (2001) The solubility of alpha-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson’s disease. Neurochemistry 76:87–96

    Article  CAS  Google Scholar 

  • Dickson DW, Braak H, Duda JE et al (2009) Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria. Lancet Neurol 8:1150–1157

    Article  CAS  PubMed  Google Scholar 

  • Gilman S, Wenning GK, Low PA et al (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71(9):670–676. doi:10.1212/01.wnl.0000324625.00404.15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halliday G, Stevens C (2011) Glia: initiators and progressors of pathology in Parkinson’s disease. Mov Disord 26:6–17. doi:10.1002/mds.23455

    Article  PubMed  Google Scholar 

  • Jellinger KA (2003) Neuropathological spectrum of synucleinopathies. Mov Disord 18(Suppl 6):S2–S12

    Article  PubMed  Google Scholar 

  • Jellinger KA (2014) Neuropathology of multiple system atrophy: new thoughts about pathogenesis. Mov Disord 29:1720–1741. doi:10.1002/mds.26052

    Article  CAS  PubMed  Google Scholar 

  • Kertesz A, Davidson W, Munoz DG (1999) Clinical and pathological overlap between frontotemporal dementia, primary progressive aphasia and corticobasal degeneration: the pick complex. Dement Geriatr Cogn Disord 10:46–49

    Article  PubMed  Google Scholar 

  • Kertesz A, Martinez-Lage P, Davidson W, Munoz DG (2000) The corticobasal degeneration syndrome overlaps progressive aphasia and frontotemporal dementia. Neurology 55:1368–1375

    Article  CAS  PubMed  Google Scholar 

  • Kwekkeboom J (2012) Modulation of dendritic cells and regulatory T cells by naturally occurring antibodies. Adv Exp Med Biol 750:133–144

    Article  CAS  PubMed  Google Scholar 

  • Litvan I, Agid Y, Calne D et al (1996) Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele–Richardson–Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 47:1–9

    Article  CAS  PubMed  Google Scholar 

  • Maetzler W, Berg D, Synofzik M et al (2008) Autoantibodies against amyloid and glial-derived antigens are increased in serum and cerebrospinal fluid of Lewy body-associated dementias. J Alzheimers Dis 26:171–179

    Google Scholar 

  • Maetzler W, Berg D, Synofzik MA et al (2011) Autoantibodies against amyloid and glial-derived antigens are increased in serum and cerebrospinal fluid of Lewy body-associated dementias. J Alzheimers Dis 26:171–179

    CAS  PubMed  Google Scholar 

  • Maetzler W, Apel A, Langkamp M et al (2014) Comparable autoantibody serum levels against amyloid- and inflammation-associated proteins in Parkinson’s disease patients and controls. PLoS One 21:e88604. doi:10.1371/journal.pone.0088604

    Article  Google Scholar 

  • Masliah E, Rockenstein E, Mante M et al (2011) Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease. PLoS One 6:e19338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKeith IG, Dickson DW, Lowe J et al (2005) Consortium on DLB. Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology 65:1863–1872

    Article  CAS  PubMed  Google Scholar 

  • Monahan AJ, Warren M, Carvey PM (2008) Neuroinflammation and peripheral immune infiltration in Parkinson’s disease: an autoimmune hypothesis. Cell Transplant 17:363–367

    PubMed  Google Scholar 

  • Nguyen T, Mehta NR, Conant K et al (2009) Axonal protective effects of the myelin associated glycoprotein. J Neurosci 29:630–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orr C, Rowe D, Mizuno Y et al (2005) A possible role for humoral immunity in the pathogenesis of Parkinson’s disease. Brain 128:2665–2674

    Article  PubMed  Google Scholar 

  • Papachroni KK, Ninkina N, Papapanagiotou A et al (2007) Autoantibodies to alpha-synuclein in inherited Parkinson’s disease. J Neurochem 101:749–756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papuć E, Kurzepa J, Kurys-Denis E et al (2014) Humoral response against glial derived antigens in Parkinson’s disease. Neurosci Lett 566:77–81

    Article  PubMed  Google Scholar 

  • Postuma RB, Berg D, Stern M et al (2015) MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 30:1591–1601. doi:10.1002/mds.26424

    Article  PubMed  Google Scholar 

  • Rajabally YA, Martey J (2011) Neuropathy in Parkinson’s disease. Prevalence and determinants. Neurology 77:1947e50

  • Seidel K, Mahlke J, Siswanto S et al (2015) The brainstem pathologies of Parkinson’s disease and dementia with Lewy bodies. Brain Pathol 25:121–135. doi:10.1111/bpa.12168

    Article  PubMed  Google Scholar 

  • Song YJ, Lundvig DM, Huang Y et al (2007) p25alpha relocalizes in oligodendroglia from myelin to cytoplasmic inclusions in multiple system atrophy. Am J Pathol 171:1291–1303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toth C, Breithaupt K, Ge S et al (2010) Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson disease. Ann Neurol 68:28e36

  • Vekrellis K, Stefanis L (2012) Targeting intracellular and extracellular alpha-synuclein as a therapeutic strategy in Parkinson’s disease and other synucleinopathies. Expert Opin Ther Targets 16:421–432

    Article  CAS  PubMed  Google Scholar 

  • Wakabayashi K, Hayashi S, Yoshimoto M et al (2000) NACP/alpha-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson’s disease brains. Acta Neuropathol (Berl) 99:14–20

    Article  CAS  Google Scholar 

  • Wenning GK, Jellinger KA (2005) The role of alpha-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol 109:129–140

    Article  CAS  PubMed  Google Scholar 

  • Wootla B, Watzlawik JO, Warrington AE et al (2015) Naturally occurring monoclonal antibodies and their therapeutic potential for neurologic diseases. JAMA Neurol 72:1346–1353. doi:10.1001/jamaneurol.2015.2188

  • Yamada T, McGeer PL, McGeer EG (1992) Appearance of paired nucleated, Tau-positive glia in patients with progressive supranuclear palsy brain tissue. Neurosci Lett 135:99–102

    Article  CAS  PubMed  Google Scholar 

  • Yamada T, Calne DB, Akiyama H et al (1993) Further observations on Tau-positive glia in the brains with progressive supranuclear palsy. Acta Neuropathol (Berl) 85:308–315

    Article  CAS  Google Scholar 

  • Yanamandra K, Gruden M, Casaite V et al (2011) a-Synuclein reactive antibodies as diagnostic biomarkers in blood sera of Parkinson’s disease patients. PLoS 25:e18513

    Article  Google Scholar 

Download references

Acknowledgments

The study received financial support from a University Grant of the Medical University of Lublin, Poland (Grant Number 387/2015).

Author information

Authors and Affiliations

  1. Department of Neurology, Medical University of Lublin, 8 Jaczewskiego Str., 20-954, Lublin, Poland

    Ewa Papuć & Konrad Rejdak

Authors
  1. Ewa Papuć
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Konrad Rejdak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ewa Papuć.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Papuć, E., Rejdak, K. Anti-MAG autoantibodies are increased in Parkinson’s disease but not in atypical parkinsonism. J Neural Transm 124, 209–216 (2017). https://doi.org/10.1007/s00702-016-1632-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-016-1632-4

Keywords

Search

Navigation