Dysfunction of the blood-cerebrospinal fluid-barrier and N-methyl-D-aspartate glutamate receptor antibodies in dementias.
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.
Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany. mandy.busse@gmx.de.
Mandy
M
Busse
Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
Ralf
R
Kunschmann
Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
Henrik
H
Dobrowolny
Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
Jessica
J
Hoffmann
Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.|Center for Behavioral Brain Sciences, Magdeburg, Germany.
Bernhard
B
Bogerts
Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
Johann
J
Steiner
Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.|Department of Psychiatry and Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Thomas
T
Frodl
Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
Stefan
S
Busse
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000134:cerebrospinal fluid*; D001812:Blood-Brain Barrier / Q000473:pathology*; D003704:Dementia / Q000134:cerebrospinal fluid / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*
D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate
Alzheimer’s disease (AD); Blood-CSF-barrier (B-CSF-B); Frontotemporal dementia (FTD); Mild cognitive impairment (MCI); NMDA-R antibodies; NMDA-R dementia; Subcortical ischemic vascular dementia (SIVD)