title: Seroprevalence of N-methyl-D-aspartate glutamate receptor (NMDA-R) autoantibodies in aging subjects without neuropsychiatric disorders and in dementia patients.
abstract: N-methyl-D-aspartate glutamate receptors (NMDA-R) play a key role in learning and memory. Therefore, they may be involved in the pathophysiology of dementia. NMDA-R autoantibodies directed against the NR1a subunit of the NMDA-R, which were first identified as a specific marker for a severe form of encephalitis, cause a decrease in NMDA-Rs, resulting in cognitive impairment and psychosis. We examined the prevalence of NR1a NMDA-R autoantibodies in the serum and cerebrospinal fluid (CSF) of 24 patients with Alzheimer's disease (AD), 20 patients with subcortical ischemic vascular dementia (SIVD), and 274 volunteers without neuropsychiatric disorder. The latter cases showed an association of seropositivity with age. Notably, the overall seroprevalence was not statistically different between dementia patients and matched controls. Further analysis of the patient samples showed that four patients with AD and three patients with SIVD had positive NMDA-R IgM, IgG, and/or IgA autoantibody titers in serum. These patients suffered from psychosis (with the exception of one case). CSF samples were negative for NMDA-R autoantibodies. We conclude that the seroprevalence of NMDA-R-directed autoantibodies is age-related. It has to be clarified by larger studies whether NMDA-R autoantibodies in peripheral blood may predispose patients with AD and SIVD to susceptibility for psychotic episodes if disturbances of blood-brain-barrier integrity occur.
authors.affiliation: Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany, stefan.busse@med.ovgu.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Busse
authors.forename: Mandy
authors.initials: M
authors.lastname: Busse
authors.forename: Britta
authors.initials: B
authors.lastname: Brix
authors.forename: Christian
authors.initials: C
authors.lastname: Probst
authors.forename: Axel
authors.initials: A
authors.lastname: Genz
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.forename: Winfried
authors.initials: W
authors.lastname: Stoecker
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003704:Dementia / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000276:immunology; D005260:Female; D005858:Germany; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000097:blood / Q000209:etiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate