| dc.contributor.advisor | Bayer, Thomas A. Prof. Dr. | |
| dc.contributor.author | Ueberück, Maximilian | |
| dc.date.accessioned | 2019-03-25T09:18:17Z | |
| dc.date.available | 2019-04-03T22:50:02Z | |
| dc.date.issued | 2019-03-25 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-002E-E5E2-0 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7363 | |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Passive Immunisierung mit einem N-trunkierten Abetaspezifischen Antikörper - Therapeutisches Potential von NT4X in einem familiären Alzheimer-Mausmodell | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | Passive immunisation with a N-truncated abeta specific antibody - therapeutic potential of NT4X in a familial Alzheimer mouse model | de |
| dc.contributor.referee | Jarry, Hubertus Prof. Dr. | |
| dc.date.examination | 2019-03-26 | |
| dc.description.abstracteng | Abstract
Alzheimer’s disease is a progressive neurodegenerative illness whose patients suffer from memory loss, problems managing everyday life and increasing helplessness. Worldwide there is a prevalence of over 47 million patients and an ever growing incidence so that Alzheimer’s disease not only presents a social and familial but also an economic problem.
For this Thesis a familial mouse model for Alzheimer’s disease was used. The 5XFAD mouse model shows a characteristic pathological development which starts with intraneuronal accumulation at around 6 weeks of age. Over the course of the following months the mice also develop neuroinflammation, a lowered neurogenesis and ultimately a loss of neurons and synapses.
The monoclonal antibody NT4X is a specific abeta antibody which has a high affinity to different soluble N-truncated abeta oligomere while having a low affinity to plaques. It was observed that NT4X has the highest binding affinity to Aβ4-x.
Patients with Alzheimer disease show, next to full-length abeta, a variety of N-truncated abeta version with N-truncated pyroglutamate Aβ3-42 and Aβ4-x being one of the most abundant forms. However, Aβ4-42 has not been considered as a therapeutic target yet.
In this thesis, the binding patterns of NT4X in human tissue was compared to well known antibodies such as Solanezumab (BS). It could be demonstrated again that the NT4X-antibody doesn’t have a high affinity to plaques. Lately it is hypothesized that plaques are thought to be inert and the soluble oligomere are the most toxic components instead the NT4X-antibody seems to be a promising therapeutical approach.
The binding profile of NT4X was characterized in the western blots. Here the antibody showed a binding profile to the N-truncated variations of abeta Aβ4-42 and pyroglutamate Aβ3-42 as well as Aβ4-40 and to a lower extent also to Aβ1-42.
The NT4X-antibody has previously been tested in a therapeutical way in the 5XFAD mouse model starting with 5 month old animals. The aim of the present Thesis was to test the NT4X in a preventative manner. The animals were treated weekly for 10 weeks starting at 6 weeks of age and the plaque load of the immunized mice was studied..
It was demonstrated that the NT4X-antibody has the capability to lower the plaque load significantly of Aβ4-x and the core of the amyloid plaques, shown by the staining with thioflavin. It also showed the trend to lower the plaque load of pyroglutamate Aβ3-42 and Aβ1-x.
The fact that the results of this preventative Thesis show a greater effect than the therapeutical intervention starting at a later stage underlines that the point of intervention is crucial.
The results of this Thesis show that NT4X works well in the 5XFAD mouse model in a preventative approach and it remains to be seen if this antibody also works in human. | de |
| dc.contributor.coReferee | Oppermann, Martin Prof. Dr. | |
| dc.subject.eng | Alzheimer's disease | de |
| dc.subject.eng | NT4X | de |
| dc.subject.eng | beta amyloid | de |
| dc.subject.eng | amyloid hypothesis | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-002E-E5E2-0-6 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Neurologie - Allgemein- und Gesamtdarstellungen (PPN619876247) | de |
| dc.subject.gokfull | Psychiatrie (PPN619876344) | de |
| dc.description.embargoed | 2019-04-03 | |
| dc.identifier.ppn | 1666649503 | |