dc.contributor.advisor | Ehrenreich, Hannelore Prof. Dr. Dr. | |
dc.contributor.author | Zerche, Maria | |
dc.date.accessioned | 2018-07-18T06:44:19Z | |
dc.date.available | 2018-07-26T22:50:03Z | |
dc.date.issued | 2018-07-18 | |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-002E-E454-5 | |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-6967 | |
dc.language.iso | deu | de |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject.ddc | 610 | de |
dc.title | Einfluss von Anti-NMDA-Rezeptor-NR1-Autoantikörpern bei ApoE4-bedingter chronischer Beeinträchtigung der Blut-Hirn-Schranke | de |
dc.type | doctoralThesis | de |
dc.title.translated | Role of anti-NMDA-receptor NR1 autoantibodies depending on ApoE4 related chronic impairment of the blood brain barrier | de |
dc.contributor.referee | Ehrenreich, Hannelore Prof. Dr. Dr. | |
dc.date.examination | 2018-07-19 | |
dc.description.abstracteng | Anti-N-methyl-D-aspartate-receptor subunit 1 autoantibodies (NMDAR-NR1-AB) have mainly been described in context of central nervous system (CNS) pathologies. In contrast, recent studies reported high seroprevalence of NMDAR-NR1-AB in both healthy and neuropsychiatrically ill subjects. It was hypothesized that this might be due to the significance of the blood-brain barrier (BBB) for both development and potential effects of CNS-reactive AB. Apolipoprotein E4 (ApoE4) represents a genetic risk factor for a chronically impaired BBB. Therefore, the present study investigates the role of NMDAR-NR1-AB depending on ApoE4-related chronic impairment of the BBB.
ApoE genotype and NMDAR-NR1-AB seropositivity were determined in a cohort of 2492 neuropsychiatric patients and healthy control subjects as well as a second cohort of 464 patients with acute ischemic stroke of the middle cerebral artery.
A high seroprevalence of NMDAR-NR1-AB independent of disease status could be replicated and extended to older age groups. The interaction of APOE4 carrier status and NMDAR-NR1-AB seropositivity was found to be significantly associated with the diagnosis of schizoaffective disorder. In patients with acute ischemic stroke, pre-existing NMDAR-NR1-AB were found to modulate the evolution of lesion size in diffusion-weighted magnetic resonance imaging (DW-MRI).
The present results demonstrate the importance of BBB integrity for the influence of NMDA-NR1-AB. Both projects provide evidence of ApoE4-related chronic BBB disruption mediating pathological NMDAR-NR1-AB effects not occurring in patients with an intact BBB. Furthermore, first data for beneficial effects of circulating CNS-reactive AB is provided supporting the concept of physiological autoimmunity. | de |
dc.contributor.coReferee | Liman, Jan Dr. | |
dc.contributor.thirdReferee | Meyer, Thomas Prof. Dr. | |
dc.subject.ger | Anti-NMDA-Rezeptor-NR1-Autoantikörper | de |
dc.subject.ger | ApoE4 | de |
dc.subject.ger | Blut-Hirn-Schranke | de |
dc.subject.ger | Schizoaffektive Störung | de |
dc.subject.ger | Ischämischer Schlaganfall | de |
dc.subject.eng | Anti-NMDA-receptor subunit 1 autoantibodies | de |
dc.subject.eng | ApoE4 | de |
dc.subject.eng | blood brain barrier | de |
dc.subject.eng | schizoaffective disorder | de |
dc.subject.eng | ischemic stroke | de |
dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-002E-E454-5-2 | |
dc.affiliation.institute | Medizinische Fakultät | de |
dc.subject.gokfull | Neurologie - Allgemein- und Gesamtdarstellungen (PPN619876247) | de |
dc.subject.gokfull | Psychiatrie (PPN619876344) | de |
dc.description.embargoed | 2018-07-26 | |
dc.identifier.ppn | 102726008X | |