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Dysfunction of the blood-cerebrospinal fluid-barrier and N-methyl-d-aspartate glutamate receptor antibodies in dementias

  • Mandy BusseEmail author
  • Ralf Kunschmann
  • Henrik Dobrowolny
  • Jessica Hoffmann
  • Bernhard Bogerts
  • Johann Steiner
  • Thomas Frodl
  • Stefan Busse
Original Paper

Abstract

N-Methyl-d-aspartate glutamate receptor (NMDA-R) antibodies (Abs) could play a role in neurodegenerative disorders. Since, in these diseases, NMDA-R Abs were detected in serum, but only sporadic in cerebrospinal fluid (CSF), the origin and impact of the Abs are still unresolved. We examined the presence of NMDA-R Abs in serum and CSF using a cell-based immunofluorescence assay as well as the function of the blood-CSF-barrier (B-CSF-B) by determination of Q albumin (ratio of albumin in CSF and serum) in patients with mild cognitive impairment (MCI; N = 59) and different types of dementia, Alzheimer’s disease (AD; N = 156), subcortical ischemic vascular dementia (SIVD; N = 61), and frontotemporal dementia (FTD; N = 34). Serum IgA/IgM NMDA-R Abs and/or a disturbed B-CSF-B were sporadically present in all investigated patients’ groups. In AD, these Abs often developed during the disease course. Patients with either no hippocampal atrophy and/or no AD-related characteristic changes in CSF, referred to “non-classical” AD, were characterized by seropositivity at diagnosis and loss of function of the B-CSF-B showed a progressive decline in cognitive functions and a poor prognosis. Our data indicate that NMDA-R Abs are present in different types of dementia and elderly healthy individuals. In combination with disturbed B-CSF-B integrity, they seem to promote their pathological potential on cognitive decline, and thus, a subgroup of dementia patients with these unique characteristics might inform clinicians.

Keywords

NMDA-R antibodies Blood-CSF-barrier (B-CSF-B) NMDA-R dementia Alzheimer’s disease (AD) Subcortical ischemic vascular dementia (SIVD) Frontotemporal dementia (FTD) Mild cognitive impairment (MCI) 

Notes

Acknowledgements

We are grateful to Bianca Jerzykiewicz and Kathrin Paelchen for their assistance in collecting samples.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

406_2017_768_MOESM1_ESM.doc (53 kb)
Supplementary material 1 (DOC 53 KB)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Mandy Busse
    • 1
    Email author
  • Ralf Kunschmann
    • 1
  • Henrik Dobrowolny
    • 1
  • Jessica Hoffmann
    • 1
  • Bernhard Bogerts
    • 1
    • 2
  • Johann Steiner
    • 1
  • Thomas Frodl
    • 1
    • 3
  • Stefan Busse
    • 1
  1. 1.Department of Psychiatry and PsychotherapyUniversity of MagdeburgMagdeburgGermany
  2. 2.Center for Behavioral Brain SciencesMagdeburgGermany
  3. 3.Department of Psychiatry and Institute of NeuroscienceTrinity College DublinDublinIreland

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