Neuroinflammation and amyloid-β in early Alzheimer’s disease: Insight into the earliest events using mouse models

Project: Dissertation

Project Details

Layman's description

Alzheimer's disease is the most common cause of dementia, but there is no effective treatment to prevent nor slow the development of the disease. Amyloid-beta is a protein that aggregates into plaques and is a hallmark of the disease. This leads many scientists to believe that these plaques, which appear outside of cells, cause Alzheimer’s disease. Recent treatments that have or are seeking regulatory approval aim to decrease this extracellular amyloid-beta plaque load, but these treatments have only moderately succeeded in improving the brain function. Therefore, it is important to consider what keeps Alzheimer’s treatments from having a bigger impact on the disease, such as whether treatments can work on different aspects or at the earliest stages of the disease. An increasing number of studies have shown that numerous changes happen in the brain before plaque formation and that factors in the brain's immune system play a bigger role in driving the disease than previously believed. In our research, we observed and emphasized an initial accumulation of amyloid-beta inside of neurons before plaque appearance. This amyloid-beta can impact the function of neurons negatively, which at a large enough scale can impair brain function. Additionally, we and others have noticed that the immune cells and immune environment of the brain are altered in the pre-plaque phase of disease models. These observations have led to the present work as we asked whether there is a connection between amyloid-beta accumulation in neurons and inflammatory changes before plaques appear. Ultimately, an increased understanding of this and the earliest events of Alzheimer’s disease development may contribute to more effective future Alzheimer's treatments.
StatusFinished
Effective start/end date2019/04/012023/10/10

UKÄ subject classification

  • Cell and Molecular Biology
  • Neurosciences