A specific type of cells, senescent cells, are damaged cells in the body that do not die when they should. These cells may possibly contribute to the development of Alzheimer's. The APOE4 genetic mutation causes an increased risk of developing Alzheimer's disease, but it is unclear why this mutation causes an increased risk. The Veni study is investigating how the APOE4 mutation can affect the formation of senescent cells and whether this process can be reversed.
APOE4 and Alzheimer's disease
In Alzheimer's disease, amyloid plaques and tau protein tangles form in brain tissue. These are abnormal protein accumulations of the proteins amyloid-beta and tau. The APOE gene plays a role in the connection between fats and proteins and is involved in the transport of fats between brain cell types. Carriers of the APOE4 mutation in the APOE gene are up to 14 times more likely to develop Alzheimer's disease.
Researching APOE4 and cell aging
Feringa will study the brain's support cells, called astrocytes. Feringa is developing these support cells from stem cells made from donor skin cells. By modifying the DNA, Feringa can see what effect the APOE4 mutation has on these cells; and how the mutation contributes to the development of senescent cells. Thanks to this technique, Feringa can see for the first time the role of the risk mutation on the aging of support cells in the brain.
This research design by Feringa will give us a lot of information about the underlying mechanisms involved in cellular aging in brain cells and possibly new leads for therapy. "By understanding how this mutation contributes to cell aging and subsequently the onset of Alzheimer's disease, I expect to find new targets for therapy directed against the development of the disease," Feringa said. The cells will be used to test more than 2,000 existing drugs to see which compounds can potentially reverse the effect on cell aging and are potentially interesting for treating Alzheimer's disease.
Veni
The Netherlands Organization for Scientific Research (NWO) has awarded Femke Feringa Veni funding. This will allow her to further develop her own research into the origin of Alzheimer's disease over the next three years.
The NWO Talent Program gives researchers the freedom to conduct their own research based on creativity and passion. They receive a maximum of 280,000 euros. The program stimulates innovation and curiosity. Free research contributes to and prepares us for tomorrow's society. This is why NWO focuses on a diversity of scientists, domains and backgrounds. Together with the Vidi and Vici grants, Veni is part of the Talent Program.
NWO selects researchers based on the scientific quality and innovative nature of the research proposal, the scientific and/or societal impact of the proposed project, and the quality of the researcher.