- Author
- Title
- Glial cells and neuronal function in Alzheimer's disease
- Supervisors
- Award date
- 13 October 2020
- Number of pages
- 227
- ISBN
- 9789493184565
- Document type
- PhD thesis
- Faculty
- Faculty of Science (FNWI)
- Institute
- Swammerdam Institute for Life Sciences (SILS)
- Abstract
-
In this thesis, we investigated the impact of Alzheimer’s disease on neuronal function and glial cells. Hereto we used various models, i.e. the APPswePS1dE9 AD mouse model, human post-mortem brain material, and a microglia-like cell model. In a review we focused on the role of reactive astrocytes in the AD mouse model, indicating that reactive astrocytes can be a promising treatment target in AD. Using the same mouse model, we investigated changes in neuronal function at various ages. We concluded that aging has a more prominent effect on the measurements than the increased presence of amyloid. In a first experiment, to investigate the potential role of microglia in AD, we used a microglia-like model to examine the effect of Aβ1-42 oligomers on transcriptomic changes. Interestingly, we observed a distinct upregulation of metallothionein subtypes in the Aβ1-42 oligomer stimulated cells. The upregulation of metallothioneins could have a neuroprotective function against the oxidative stress and neuroinflammation involved in AD, indicating that the acute activation by Aβ1-42 oligomers could induce a protective response.
We characterized the Aβ plaque burden and morphology in cortical brain slices of AD patients and non-demented control with amyloid plaques. Even though the last group has overall less Aβ plaques, relatively more dense-core plaques were observed. We found no differences in the total number of microglia or morphology between the groups. Further characterization of plaque-associated microglia suggested a reduced phagocytic activity by microglia surrounding dense-core plaques in NDC+-cases. No difference in synaptic density between AD- and NDC+-cases near dense-core or diffuse plaques was detected. - Persistent Identifier
- https://hdl.handle.net/11245.1/01f56fd0-fe11-4698-a86e-09bb34aefe33
- Downloads
-
Thesis (complete)
Front matter
Scope
Chapter 1: Reactive astrocytes as treatment targets in Alzheimer’s disease: Systematic review of studies using the APPswePS1dE9 mouse model
Chapter 2: Modulating astrocyte function in acute hippocampal slices from the mouse, a technical note
Chapter 3: Age dependent changes in cellular excitability and synaptic plasticity in CA1 pyramidal neurons in APPswePS1dE9 mice
Chapter 4: Transcriptomic and functional analysis of Aβ₁⁃₄₂ oligomer-stimulated human monocyte-derived microglia-like cells: Revealing a role for metallothioneins
Chapter 5: Amyloid plaques in the temporal cortex of non-demented controls are often dense-core plaques and contain less CD68⁺ plaque-associated microglia compared to Alzheimer’s disease patients
Chapter 6: Summary and general discussion
Nederlandse samenvatting; Dankwoord; Curriculum vitae
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