The onset of Alzheimer's disease has been linked to the accumulation of fat in the brain
Scientists from the USA have found a new understanding of the causes of Alzheimer's disease. They believe that the main factor is related to the accumulation of fat droplets in brain cells.
Alzheimer's disease is considered one of the most common forms of dementia, which is usually found in people over 65 years old. But there is also an early form of the disease, which is rarer. As of 2006, the total incidence of Alzheimer's disease was estimated at 26.6 million people. That number is expected to quadruple by 2050.
The disease begins with short-term memory loss and ends with global failures in long-term memory. The causes of the disease are still not clear. There are many hypotheses about it. One of them states that the main factor in the development of this disease is the deposition of beta-amyloid in brain tissue. According to another hypothesis, the cascade of disorders is triggered by abnormalities in the structure of the so-called tau protein, which is often found in neurons of the central nervous system.
The debate over which of these two proteins can be called the key culprit in Alzheimer's disease has been going on for decades. The first hypothesis leads the way because some treatments targeting beta-amyloid show a slowing of memory loss. There is also speculation about the infectious nature of the disease.
Scientists from Stanford University (USA) have proposed a new concept explaining the occurrence of Alzheimer's disease. They drew attention to the fact that at the beginning of the last century German psychiatrist and neurologist Alois Alzheimer, in honor of whom the disease was named, noticed in the brain of deceased patients amyloid plaques, tau-proteins and drops of fat. However, no one usually paid attention to the droplets themselves. Researchers from the US did, and presented their findings in the journal Nature.
The team of scientists studied the most important genetic risk factor for the development of the disease - a gene called APOE. The protein it encodes helps transport fat in and out of cells. There are different variants of this gene: some carry less risk of developing the disease, while others carry more. Why this is the case is unclear.
To determine which proteins are produced in individual brain cells, scientists used single-cell RNA sequencing. Experiments were conducted on tissue samples of people who died of Alzheimer's disease and had either two copies of the variant APOE4 or two copies of APOE3.
It turned out that the key difference in the immune cells of those who had the first variant was a higher level of a certain enzyme, the effect of which was to increase the number of fat droplets in these cells. Then, using cells from living people with both gene variants, the researchers grew this type of immune cells in a dish. Applying beta-amyloid to them led to an accumulation of fatty tissue. This effect was particularly pronounced in the APOE4 variant.
The scientists concluded that in the development of Alzheimer's disease, the accumulation of beta-amyloid causes and accumulation of adipose tissue. After that, all this leads to the accumulation of tau-protein inside neurons, which provokes their death. The result is symptoms of memory loss and confusion.
It turned out that compared to people who had two copies of the gene variant with the lowest risk of developing Alzheimer's disease (APOE2), those who had one or two copies of other variants of the same gene were almost four times more likely to get the disease. That is, about 75 percent of people with Alzheimer's disease could have remained healthy if they had a different variant of the gene.