Objectives
The main purpose of the project has been to contribute to better and earlier diagnosis of Alzheimer's disease by gaining better insight into risk factors and causal relationships. To achieve this, we had two questions we investigated:
(1) Can we identify new epigenetic mechanisms that can explain brain tissue loss and cognitive impairments in Alzheimer's and the stages before the disease can be diagnosed? (2) What role does poor sleep play in brain tissue loss and cognitive impairments? Can we understand the complex relationships between epigenetics/genetics and sleep, brain tissue loss, various risk factors for Alzheimer's, and reduced memory capabilities?
The risk of dementia is largely determined by hereditary factors. However, recent research has shown that common differences in the human DNA molecule can only partially explain this heritability. In fact, much evidence suggests that epigenetic mechanisms are also important. Epigenetics involves heritable changes in DNA that do not directly affect the genetic code. Recent technological developments have enabled us to examine for the first time how such epigenetic markers relate to other risk factors for Alzheimer's, which, for example, we can trace in brain and cerebrospinal fluid or through various types of brain imaging.
This project aimed to test the importance of epigenetics for the risk of Alzheimer's disease by conducting epigenetic and genetic analyses in samples of non-demented older individuals, as well as patients with mild cognitive impairment or Alzheimer's dementia. We would further relate this to sleep problems, including through an experiment where we directly test the effect of sleep on memory and the role of epigenetic/genetic mechanisms.
Results
We have found, among other things, that more self-reported sleep problems are associated with the accumulation of beta-amyloid in the cerebral cortex, which is associated with a higher risk of Alzheimer's dementia. We have also investigated which genes are typically expressed in these areas where sleep problems are related to beta-amyloid.
Furthermore, we found that participants who report more sleep problems experience more hippocampal and specific cerebral cortex tissue loss over time. These effects overlap with areas characterized by strong expression of genes for oligodendrocytes, which are responsible for producing and maintaining the insulation of brain nerve connections. We also see that genetic risk factors for sporadic Alzheimer's seem to affect hippocampal volume throughout life and do not have the greatest effect in older age.
Related to the project are also our new findings that neuroinflammation is associated with more atrophy - tissue loss - in brain regions associated with Alzheimer's disease. This association was completely independent of the amount of amyloid participants had in their brains but seemed to be related to a higher occurrence of tau.
Publications
Associations of circulating C-reactive proteins, APOE ε4, and brain markers for Alzheimer's disease in healthy samples across the lifespan. Brain Behav.Immun 2022.
Financing
Nasjonalforeningen for folkehelse grant nr. 7333.