Therapiemöglichkeiten der Alzheimer-Krankheit durch passive Immunisierung mit dem NT4X-Antikörper im Tg4-42hom-Mausmodell

Alzheimer therapy with passive immunization using the antibody NT4X in Tg4-42hom mice

by Henning Borgers
Doctoral thesis
Date of Examination:2017-07-04
Date of issue:2017-07-05
Advisor:Prof. Dr. Thomas A. Bayer
Referee:Prof. Dr. Thomas Dresbach
Referee:Prof. Dr. Martin Oppermann
Persistent Address: http://dx.doi.org/10.53846/goediss-6363

 

 

Files in this item

Name:Dissertation_Henning_Borgers.pdf
Size:1.94Mb
Format:PDF

The following license files are associated with this item:

Abstract

English

Aβ4-42 is one of the major variants of beta-amyloid (Aβ) in the Alzheimer brain and one of the earliest to appear in the development of the disease. It shows an increased aggregation tendency and toxicity. Furthermore it has been shown previously, that Aβ4-42 also affects brain functions and induces cognitive impairments in vivo after intraventricular injection to the brain of wildtype mice and in Tg4-42 mice. These mice carry a transgene for an enhanced expression of Aβ4-42 and develop a severe neuron loss in the CA1 region of the hippocampus that correlates with age-dependent memory deficits. Nevertheless, Aβ4-42 has not been considered as a therapeutic target yet. This study analyzes the progression of cognitive deficits in the brain of Tg4-42 mice to detect the best time to start a treatment. It then demonstrates that passive immunization with the antibody NT4X reacting with the free N-terminus of Aβ4-x and AβpE3-X but not with Aβ1-x significantly attenuates neuron loss in the hippocampus of Tg4-42 mice and rescues spatial reference memory deficits. For the first time it could be demonstrated that a preventive therapy with NT4X, which has previously been proven to rescue the toxicity of oligomeric Aβ4-42 in vitro, has therapeutically beneficial effects in an Alzheimer mouse model in vivo, which emphasizes the meaning of Aβ4-42 as a possible target in the treatment of Alzheimer’s disease.
Keywords: Alzheimer; passive immunization; NT4X; Tg4-42; CA1; neuron loss
Schlagwörter: Alzheimer; Passive Immunisierung; NT4X; Tg4-42; CA1; Nervenzellverlust
 
Statistik