海角社区

What is the title of your thesis?

“Cerebral impact of E.coli infections and bacterial proteins on neuroinflammation, Aβ homeostasis, spatial learning and memory – a possible link to development and progression of Alzheimer´s disease”.

At which department and/or research unit did you complete your PhD?

Neurobiological research, Department of Molecular Medicine, Faculty of Health Sciences, 海角社区.

Who was your principal supervisor?

Bente Finsen, Professor, MD, DMSc.

What question did you aim to answer with your thesis?

A disruption of Aβ homeostasis, in which the production of Aβ peptides exceeds their clearance and degradation, leads to an accumulation of Aβ in the brain, which is a key feature of Alzheimer’s disease.

I investigated whether E. coli and bacterial proteins can influence neuroinflammation, the Aβ balance in the brain, as well as learning and spatial memory in ways that may be significant for the development and progression of Alzheimer’s disease.

What did you find?

The thesis demonstrates that both live E. coli and bacterial proteins can influence the brain’s inflammatory response as well as Aβ levels. In transgenic Alzheimer’s mouse models, increased Aβ42 levels were observed in both the acute and subacute phases following infection, and in older animals also an increased Aβ plaque load in the acute phase.

Mice displaying more severe sickness behaviour had either a higher Aβ plaque load or higher Aβ levels in the insoluble fibril/plaque fraction. Wild-type mice remained largely unaffected.

Our data suggest that the effects of infections on inflammation and Aβ are transient and appear to depend, among other factors, on disease stage (age) and the severity of the infection (bacterial concentration and virulence factors), and require a persistent bacterial presence in the central nervous system as well as an already established Aβ plaque pathology.

Furthermore, our findings raise the possibility that repeated or chronic exposures, rather than single acute events, may be necessary to generate long-term pathological and/or behavioural changes in older transgenic mice.

How did you do it?

The thesis is primarily based on experimental studies in mouse models. I investigated the effects of both live E. coli, the bacterial amyloid protein CsgA, and the endotoxin LPS in transgenic Alzheimer’s mice, wild-type mice, and TNF knockout mice of different ages.

In addition, I used microglial cell cultures, measured markers of inflammation and Aβ peptides, and examined spatial learning and memory, among other methods using the Barnes maze.

How can your research be applied (in the clinic, society, etc.)?

The research contributes to a more nuanced understanding of how bacterial infections, bacterial proteins, and inflammatory signalling pathways may influence processes relevant to Alzheimer’s disease.

The findings cannot be directly translated into clinical practice at present, but they suggest that factors such as the severity of infections and/or continuous or repeated exposures over time, as well as their behavioural consequences, should be considered in future studies.

In the longer term, this may contribute to a better understanding of risk factors and disease-modifying mechanisms in sporadic Alzheimer’s disease.