Probing the role of oligodendrocytes in Alzheimer’s disease While the development of Alzheimer’s disease has historically been associated mainly with the loss of neuronal connections in the brain, evidence suggests that the loss of myelin-producing cells called oligodendrocytes is also an important factor. We spoke to Dr Sarah Jaekel about her research into the role of oligodendrocytes in the pathology of Alzheimer’s disease. The progression of Alzheimer’s disease has historically been associated mainly with the loss of neuronal connections in the brain, yet recent research suggests that changes in cells called oligodendrocytes also play an important role. Oligodendrocytes produce myelin, which effectively insulates neuronal axons in the body in a process called myelination. “Myelin is produced soon after birth, but myelination is actually a very slow process. Myelin is produced until you are around 40 years old, and then it degrades as part of the aging process,” explains Dr Sarah Jaekel, head of a research laboratory at the hospital of the Ludwig Maximillian University (LMU) of Munich. Alongside their role in producing myelin, oligodendrocytes also have additional functions. “Oligodendrocytes also provide metabolic support to neurons,” explains Dr Jaekel. While previously it was thought that all oligodendrocytes had the same function, it is now recognised that they are in fact quite heterogenous. “There are sub-sets of oligodendrocytes, which seem to be doing different things,” says Dr Jaekel. Deciphering the Role of Oligodendrocytes in the Pathogenesis of Alzheimer’s Disease This project is funded by the Deutsche Forschungsgemeinschaft (DFG), Emmy Noether. Dr. Sarah Jaekel Institute for Stroke and Dementia Research Feodor-Lynen-Str. 17 D-81377 Munich T: +49 (0) 89 / 4400-46238 E: sarah.jaekel@med.uni-muenchen.de W: https://www.isd-research.de/ research-groups/ jakellab/50781cbb75d49b45 Dr Sarah Jaekel is the leader of a research group focusing on oligodendrocyte pathology at LMU. She studied biochemistry at Ulm University and held positions at LMU and the University of Edinburgh, before gaining an Emmy Noether research grant in 2021.
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Oligodendrocytes in the human brain have been shown to have different states which are assumed to have different functions (exemplary shown as oligodendrocytes A-C). There is the hypothesis that these oligodendrocyte states are differently distributed across regions in the human brain. In the course of ALzheimer’s disease the environment in the brain changes and is considered toxic for cells including oligodendrocytes, however some of the states might be more vulnerable to environmental stress than others, which could explain the different vulnerability of some brain regions to Alzheimer’s disease. Illustration recreated from original figure by Dr Sarah Jaekel.
Oligodendrocytes As the head of a research project based at LMU, Dr Jaekel is now investigating these different subpopulations of oligodendrocytes and their role in the pathogenesis of Alzheimer’s disease. The idea here is that the death of oligodendrocytes in the later stages of Alzheimer’s is not just a side-effect of the disease, and that changes in these cells are in fact a co-factor. “Oligodendrocytes may play a role in disease pathogenesis, in the early stages of the
Researchers can then look to assess the impact on oligodendrocytes’ function and their ability to maintain neurons. Oligodendrocytes are known to secrete certain substances, including neurotrophic factors, which help to maintain neurons. “This is important for neuronal health,” says Dr Jaekel. The loss of myelin and damage to neurons are also features of some other conditions, and Dr Jaekel hopes to draw
My vision is to compare
oligodendrocytes in different neurological disorders. disease,” outlines Dr Jaekel. This research is highly translational, with Dr Jaekel and her colleagues using a variety of different techniques, including single nuclei RNA-sequencing to probe deeper into different populations of oligodendrocytes. “We are analysing post-mortem human brain tissue, while we are also using human induced pluripotent stem cells (iPSCs),” she says. “With iPSCs, we can add certain things to oligodendrocytes, and then look to see how they react.”
wider comparisons in future. “Multiple sclerosis is a de-myelinating condition for example, but in the late stages it becomes a neurodegenerative disorder. This is because there is no re-myelination, and the neurons degenerate and then die,” she says. “My vision is to compare oligodendrocytes in different neurological disorders, to see if they have any common pathological mechanisms.”
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