Investigating the effect of a Tumour Necrosis Factor-Alpha (TNF-α) Receptor 2 agonist on 3xTG-Alzheimer mice

Zwiers, Ilse (2025) Investigating the effect of a Tumour Necrosis Factor-Alpha (TNF-α) Receptor 2 agonist on 3xTG-Alzheimer mice. Master's Research Project 1, Biomedical Sciences.

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Abstract

Alzheimer’s disease (AD) is marked by amyloid-beta (Aβ) plaques and tau tangles, with growing evidence linking neuroinflammation to its progression. Tumour Necrosis Factor-alpha (TNF-α) plays a key role in this inflammation. Still, total TNF-α inhibition can cause harmful side effects due to its dual receptor activity: TNFR1 promotes inflammation and cell death, while TNFR2 supports cell survival and reduces inflammation. Targeting these receptors selectively may offer safer treatment options. This study explores the effects of selective TNFR2 activation in wild-type and 3xTG mouse models of AD. This was investigated by injecting the mice with a TNFR2 agonist either 6 weeks or 12 weeks. After injections, behavioural tests and immunohistochemistry were performed to assess the effects of this agonist. The results show that the agonist does not alter astrocyte or microglial activation in WT mice, nor does it affect cognition in these animals. There is a tendency toward improved hippocampal memory in agonist-treated female 3xTG mice. In addition, male mice performed better than female mice in the Morris water maze, indicating sex differences in cognition. Although extracellular plaque load was not significantly reduced in agonist-treated mice, intracellular Aβ staining was decreased in agonist-treated male mice. Lastly, working memory was not affected by the treatment compared to controls. This study shows promising results for using a TNFR2 agonist as a treatment strategy for AD; however, more research is needed to understand the heterogeneity of the human disease.

Item Type:	Thesis (Master's Research Project 1)
Supervisor name:	Eisel, U.L.M. and Bayraktaroglu, I.
Degree programme:	Biomedical Sciences
Thesis type:	Master's Research Project 1
Language:	English
Date Deposited:	11 Sep 2025 13:47
Last Modified:	11 Sep 2025 13:47
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/37024

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