Stem Cell Mitochondria – The Key to Alzheimer’s Disease Treatment

A new study showed that in Alzheimer’s disease the utilization of damaged mitochondria is impaired in neural stem cells, preventing their differentiation into new neurons. This process is probably the reason for the lack of neurogenesis in this disease, which gives scientists a new goal for creating treatment.

The main problem with Alzheimer’s is that the brain is not able to produce new neurons. In the hippocampus, a region of the brain associated with memory formation, neural stem cells (NSCs) produce new neurons throughout life. However, this does not happen with Alzheimer’s disease, which, according to scientists, leads to cognitive impairment.

Previous studies have shown that there is another problem in the brain in this disease: mitochondria that provide cells with energy can be deformed and ineffective. Cells are able to utilize damaged or old mitochondria – this process is called mitophagy. However, in impair of this function, the cells weaken and stop working properly.

A new study published in Molecular Neurobiology, conducted by scientists from Columbia University and the Ludwig Maximilian University of Munich in collaboration with NYSCF Research Institute examines in more detail the regeneration of brain cells.

The results of the study showed mitophagic disorders in NSCs affected by Alzheimer’s disease, which potentially preventing the transformation of neural stem cells into new neurons.

For a more detailed study of this problem, scientists created NSCs from stem cells of patients with a certain mutation, leading to the emergence of a familial Alzheimer’s disease (FAD), which sometimes can occur as early as a patient’s 30s or 40s. Impaired neurogenesis is a critical early sign of FAD, often appearing before the characteristic symptoms of the disease – plaques formation or neurodegeneration. The scientists also created a control population of NSCs from healthy donor cells for comparison.

The team found that in the neural stem cells of patients with familial Alzheimer’s disease, mitophagy was reduced compared to cells in healthy people. They also had lower levels of proteins responsible for autophagy (the general process of recycling organelles and macromolecules in cells). Defective mitochondria and the inability to utilize them lead to a lack of energy in stem cells and, as a result, make it difficult to convert them into neurons.

Now that scientists have found that mitophagic disorder affects neurogenesis, they plan to start developing treatments that will help NSCs effectively utilize damaged mitochondria, allowing cells to function and turn into new neurons. These treatments will focus on the critical components of Alzheimer’s disease and potentially help improve some of the symptoms.