Alzheimer’s disease is the most common cause of dementia. It is complex, and despite much research, the precise cause remains unknown. All cells in the body contain building blocks called proteins. In Alzheimer’s disease, certain proteins, such as amyloid and tau, form abnormal clumps in the brain. Another commonly seen process associated with Alzheimer’s disease is dysfunction in a part of brain cells called the mitochondria. The mitochondria act like the batteries of the cell – providing energy for the cell to efficiently function and survive. It is thought that these two processes are linked, working together to cause brain cell death and ultimately lead to the symptoms seen in Alzheimer’s disease.
Mitochondria are very important for the survival of the cell and so are highly regulated. Damaged and dysfunctional mitochondria are removed from the cell and recycled, in a process called mitophagy. Previously, it has been found that the presence of amyloid clumps can increase the recycling of the mitochondria. Furthermore, another protein called Miro1 has also been linked to the recycling of mitochondria, as well as the movement of the mitochondria through the cell. This study attempted to discover whether Miro1 plays a key role in mitochondrial recycling caused by the amyloid clumps.
The researchers grew brain cells from mice and treated them with amyloid. They found that in cells treated with amyloid, the mitochondria were less efficient at producing energy than in cells that were untreated. They also found less mitochondria in amyloid treated cells, as well as increased levels of proteins associated with mitochondrial recycling. This suggests that amyloid treatment makes mitochondria less functional and leads to an increase in mitochondrial recycling. The researchers also investigated whether Miro1 was affected by amyloid treatment and found that levels of the protein decreased with amyloid treatment.
Amyloid is known to increase the presence of highly reactive molecules in the brain called reactive oxygen species (ROS). These molecules are a natural by-product of energy production and are usually removed by proteins called antioxidants, but when their levels are increased by amyloid, the antioxidants are not able to remove them as efficiently. When a ROS scavenger, a molecule which mops up excess ROS, was given to the cells, many of the changes seen with amyloid treatment including reduced Miro1 levels, were reversed. This suggests that the effects of amyloid on the mitochondria were caused by an increase in ROS.
To determine whether the decrease in Miro1 played a key role in the other changes seen, the researchers replaced the Miro1 that had been lost in the amyloid treated cells. This was seen to reverse many of the changes that were caused by amyloid treatment.
To investigate these processes in a more complex model of Alzheimer’s disease, the researchers studied mice whose genes, which are like a blueprint for all living things, had been altered to give them Alzheimer’s like symptoms. They saw similar results in the Alzheimer’s mice as they did in the cells treated with amyloid.
The researchers concluded that amyloid increases ROS levels, which in turn increase mitochondrial recycling via a reduction in Miro1. These results improve our understanding of the relationship between Alzheimer’s disease, amyloid, and mitochondria and may help in the development of a novel therapeutic target for Alzheimer’s disease. However, further study is required to better determine the importance of Miro1 in Alzheimer’s disease.