The Role of Ferroptosis in Dementia and Loss of Navigation

Researchers Stephan Back and Philip Adeniyi at OHSU discover ferroptosis in microglia which is found to have happened in patients with dementia and Alzheimer’s. Ferroptosis is the process by which a buildup of iron kills microglia. This study was done using dead brain tissue from post-mortem dementia patients. In these patients, microglia destroyed the white matter in the brain. This suggests that with patients who have Alzheimer’s and vascular dementia, the microglia themselves are also destroyed in the process of clearing up damaged myelin. This occurs due to excess iron buildup in microglia due to myelin being iron-rich. This specifically happens in the white matter of the brain in patients with dementia and Alzheimer’s. Without doubt, the destruction of microglia in the white matter of the brain would advance the progression of dementia.

In William Yost’s talk, Spatial Memory: Neural Spatial Computations, he explains the function and creation of cognitive spatial maps. There are several types of cells involved in creating a spatial map of an animal’s position and orientation including place cells, head direction cells, grid cells, and boundary cells. Yost also mentions that olfaction and other sensory systems are dependent on position and orientation of the sensor itself. That also helps create spatial maps. Lastly, he touches on the idea that patients with dementia and Alzheimer’s could potentially lose their ability to navigate due to degrading spatial maps and loss of spatial memory.

The loss of spatial memory in dementia patients could be due to degrading white matter in the hippocampus. Since white matter is mainly axons, it could be assumed that ferroptosis happens in the hippocampus as well. Future research could be done to determine whether the loss of spatial maps is due to ferroptosis specifically in the hippocampus or other parts of the brain involved with learning and memory. Other aspects of research could involve pharmacological ways to prevent myelin degeneration or microglia death from iron buildup. It could also be tested to see whether dementia patients have difficulty with sensory systems after having trouble navigating.

References: 

Adeniyi, P.A., Gong, X., MacGregor, E., Degener-O'Brien, K., McClendon, E., Garcia, M., Romero, O., Russell, J., Srivastava, T., Miller, J., Keene, C.D. and Back, S.A. (2023), Ferroptosis of Microglia in Aging Human White Matter Injury. Ann Neurol, 94: 1048-1066. https://doi.org/10.1002/ana.26770

Hartley T, Lever C, Burgess N, O'Keefe J. Space in the brain: how the hippocampal formation supports spatial cognition. Philos Trans R Soc Lond B Biol Sci. 2013 Dec 23;369(1635):20120510. doi: 10.1098/rstb.2012.0510. PMID: 24366125; PMCID: PMC3866435.

Robinson, E. (2023, September 5). OHSU scientists discover new cause of alzheimer’s, vascular dementia . OHSU News. https://news.ohsu.edu/2023/09/05/ohsu-scientists-discover-new-cause-of-alzheimers-vascular-dementia