The “mitochondria” are the cell’s powerhouses and known to be implicated in Alzheimer’s disease. Jun.-Prof. Dr. Michela Deleidi from DZNE Tübingen and coworkers have taken a look on this relationship by studying “organoids”, which are miniature 3D brain models derived from stem cells. Their research is featured on the cover of “Molecular Psychiatry”.
They are up to four millimeters in size, float in a Petri dish and are designed to help in understanding the causes of diseases and developing therapies: three-dimensional brain organoids, grown in the laboratory from human stem cells. These little brain models develop in a similar way to a human brain. This is why they also feature mitochondria, which are tiny "powerhouses" responsible for cellular energy metabolism. If there is a defect in this process, the energy metabolism in the cells is disturbed. In some cases, such a defect has a genetic cause. As a result, so-called mitochondrial diseases occur, which manifest themselves for example in brain disorders.
The DZNE research group led by Michela Deleidi has now used such "mini-brains" to investigate the role of mitochondria in Alzheimer's disease. The researchers found that defects in the mitochondrial gene PITRM1 lead to an increase of protein deposits in the mini-brains, similar to the so-called amyloid-beta plaques observed in the brains of Alzheimer's patients. The researchers also used the mini-brain models to test medications against neurodegenerative and neuropsychiatric diseases. They found that drugs targeting the mitochondria may be useful in delaying or even preventing Alzheimer's disease. "Our study also suggests that mitochondria affect brain inflammation at the early stages of the disease," says Michela Deleidi. "Hence, medications targeting both, mitochondria and the inflammatory response, should be studied for the treatment of Alzheimer's in future studies".