Hippocampal Alterations in Alzheimer’s Disease and the Modulatory Effects of TNF Alpha

Froelich, Matteo (2025) Hippocampal Alterations in Alzheimer’s Disease and the Modulatory Effects of TNF Alpha. Bachelor's Research Project (period 2b), Biology.

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that impacts patients' memory and executive function. Characterized by amyloid-β (Aβ) plaques and neurofibrillary tau tangles, AD is extremely complex, involving many different mechanisms. A new player in this system is tumor necrosis factor-α (TNF-α), a cytokine that plays an antithetical role by promoting neuroprotection via its receptor 2 (TNFR-2) and neuroinflammation via its receptor 1 (TNFR-1). Previous research has associated TNF-α with the progression of AD, mainly attributing this to its inflammatory role, but given its dual signaling pathways, TNF-α represents a unique way to target neurodegeneration and neuroprotection pathways in AD. Accordingly, the aim of this study is to determine whether TNF-α modulation presents a viable and safe approach to combating AD. We began by assessing the effects of AD pathology on neuronal, synaptic, and oligodendrocyte markers in AD mouse model brains. Next, we explored the thermostability and cytotoxicity of a TNFR2 agonist, STAR2, using an MTT assay. Finally, the functional effects of a TNFR1 antagonist on J20 mice in a Y-maze were investigated. Our results were largely inconclusive; however, STAR2 appeared thermostable, while TNFR1 antagonism did not improve short-term memory in J20 mice. Still, given existing research, TNF-α modulation as a therapeutic for AD warrants further investigation to conclusively determine its potential disease-modifying effects.

Item Type:	Thesis (Bachelor's Research Project (period 2b))
Supervisor name:	Eisel, U.L.M.
Degree programme:	Biology
Thesis type:	Bachelor's Research Project (period 2b)
Language:	English
Date Deposited:	17 Jun 2025 07:02
Last Modified:	17 Jun 2025 07:02
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/35365

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