A recent study has found that Alzheimer’s disease risk gene damages the brain’s immune cells functioning. The gene apolipoprotein E4 (APOE4) is the most prevalent risk factor for Alzheimer’s disease.
Researchers have always found difficulty in studying human microglia, the brain immune cells. The reason was that it was difficult to isolate a sufficient number of the cells from human brain tissue.
However, in the recent study, researchers have developed a potential method to isolate patient’s stem cells. After that, they can differentiate them to produce a large amount of human microglia.
The study was conducted by the University of Eastern Finland in association with 2 other renowned universities.
Alzheimer’s disease is the leading cause of dementia in elderly people. Studies suggest that it occurs due to the accumulation of amyloid protein in the brain. However, the exact cause for this accumulation is still unknown.
Human microglia – the brain immune cells
Amyloid protein accumulation causes damage to neurons resulting in cell death and brain shrinkage. There is no treatment or therapy to slow down the progression or cure the disease. Major studies regarding treatment have focused on the prevention to avoid amyloid accumulation in the brain.
Microglia phagocytose the abnormal quantity of amyloid in the brain. They also take care of the inflammatory processes in the brain.
These functions are important in maintaining homeostasis in the brain. They also protect the brain from pathogens and regulate normal cell death that occurs with age.
However, in Alzheimer’s disease, microglia are unable to remove excess amyloid from the brain. The exact mechanism is still unknown why microglia become unable to perform their function of removing toxic amyloid.
Moreover, researchers found that microglia either lose their normal functioning or they do the opposite of the normal function. This means, in Alzheimer’s disease, they may increase the damage to the neurons.
The genetic risk factor of Alzheimer’s disease – APOE4
Apolipoprotein E4 (APOE4) is the potentially strongest risk factor for Alzheimer’s disease.
Apolipoprotein APOE is involved in the metabolism of lipids in the brain such as the metabolism of cholesterol. In this way, it helps in repairing the damage to neurons of the brain.
Apolipoprotein exists in three isoforms. The genetics determine which isoform will be present in an individual. However, only APOE4 isoform of apolipoprotein predisposes Alzheimer’s disease in an individual.
In the recent study, researchers found that APOE4 elevated the inflammatory response of microglia. However, it reduces the cells’ ability to migrate at the site and phagocytose the excess amyloid in the brain.
Researchers also found that APOE4 damages the metabolic activity of human microglia. All these findings develop a statement that APOE4 causes an intense effect on the basic functions of human microglia.
On the other hand, the study unveils an interesting observation. This states that human microglia play an important role in the progression of Alzheimer’s disease. The observation is independent of the microglia’s ability to remove accumulated amyloid protein from the brain.
The stem cell-derived microglia enable us to study different molecular mechanisms in other brain diseases. They also provide a tool for controlled studies to develop new targeted therapies.