Fat may be in the brain, not only the plates, the hidden driver of Alzheimer’s disease

Research results, published in ImmunityIt has shown that excess fat in the immune cells residing in the brain, which is called small glial cells, weakens their ability to fight the disease. This insight opens a way to biological -based neurological treatments that can treat diseases such as Alzheimer’s by enhancing the exact function and neurological health. This work was led by Guerav Chopra, James Tarbo Junior, and Margaret Tarbo, a professor of chemistry and (as a compliment) in computer science in Bordeaux.

While most of the development of Alzheimer’s disease aims to preliminary diseases of the disease-mixed protein paint called the amyloid beta and the tunece of protein Tau-Chopra focuses on the cells rich in fat abnormally surrounding the sick brain areas. In the previous work published in natureChopra and collaborators showed that in the presence of a disease, the star cells – another type of cell that supports neurons – has a toxic fat acid of the brain cells. Another cooperative work with the University of Pennsylvania, published last year in natureAlso the functional imbalance of the mitochondria in the neurons with fat deposits in the glial cells during aging – a major risk factor for nervous degeneration.

“From our point of view, targeting the paintings or tangles will not solve the problem; we need to restore the function of the immune cells in the brain,” said Chopra. “We find that reducing the accumulation of fat in the sick brain is the key, as the accumulated fat makes it difficult for the immune system to do its work and maintain balance. By targeting these paths, we can restore the ability of immune cells such as small glial cells to fight the disease and maintain the brain in the balance, which is what they do to do.”

The Chopra team worked in cooperation with researchers at Cleveland Clinic led by Dimitrius Davalus, Assistant Professor of Molecular Medicine. Chopra is also the director of the Merck-Bordeaux Center and a member of the Bordeaux Institute for Integrative Neuroscience; Bordeaux Institute for Discovery of Drugs; Bordeaux Institute for inflammation, immunity and infectious diseases; And the Regestrief Center for Health Care Engineering.

Chopra’s work is part of the Purdue Healthy Presidential Initiative, which brings together in search of human health, animal and planting. His research supports the initiative’s concentration on advanced chemistry, as Purdue is studying complex chemical systems of Purdue and developing new technologies and applications.

More than 100 years ago, Alois Alzheimer has selected deformities in the brain of a woman with the disease now bearing his name, including paintings, tangles and cells filled with drops of fatty compounds called fat. Until recently, these fat drops have been rejected as secondary products for the disease.

But the bonds that Chopra and his team found between neuromuscular diseases and fats in small glial cells and star cells – both types of glial cells that support neurons in the brain – they indicate strongly to otherwise. Chopra says this research sets the basis for a “new fat model for nervous degeneration”. He loves to call this fat accumulation “fat plaques”, because they are not like spherical drops.

“The fat drops are not pathogenic, but the accumulation of these drops is bad.

the Immunity Paper focuses on small glial cells, “intentional immune cells in the brain”, which get rid of debris, such as wrong proteins such as the amyloid and oo beta, by absorbing and breaking them through a process called phagocyto. The chopra team examined the small glial cells in the presence of the amyloid beta and asked a simple question: What happens to the small glial cells when you contact the amyloid beta?

Pictures of the brain tissue showed from people with Alzheimer’s disease, the amyloid beta plaques surrounded by small glial cells. Small glial cells contain 10 micrometers of these panels have twice the number of fat drops such as those present. These sebaceous fatty cells are the closest to the paintings that have been wiped by 40 % of the amyloid beta from the regular small glial cells of brains without disease.

In achieving the reason for the weakness of the small glial cells in the brains of Alzheimer’s, the team used specialized techniques and found that small glial cells in contact with the paintings and inflammation associated with diseases have produced a surplus of free fatty acids. While small glial cells use free fatty acids as an energy source – and some of these fatty acids are useful – Chopra and his team discovered that fatty fats closest to the amyloid bita plaques convert these free fatty acids into Trexelli Glyleren, which is a store of fat, in large quantities so that they become carried and found through their cost. The formation of these fat drops depends on age and disease, and becomes more prominent with the progress of Alzheimer’s disease.

By tracking the complex chain of steps used by Microglia to convert free fatty acids into triacelglycerol, the research team entered into the last step of this path. They found high levels abnormally from the enzyme called DGAT2 stimulates the last step to convert free fatty acids into a glycerin. They expected to see high levels of the same amount of DGAT2 gene – where the gene was copied to produce protein – but this was not the case. The enzyme accumulates because it does not decompose the speed that is usually produced, rather than excessive production. DGAT2 accumulation leads to the conversion of fatty acids to long -term storage and fat accumulation instead of using energy or repair.

“We have shown that the amyloid beta is directly responsible for the fat that is formed inside the small glial cells,” said Chopra. “Because of these sediments, the fine cells become dysfunctional – stop clearing the amyloid beta and stop their work.”

Chopra said that researchers do not yet know what causes DGAT2 enzyme. However, in their search for treatment, the team tested two molecules: one prevents the DGAT2 function and another enhances its deterioration. The deterioration of the DGAT2 enzyme was ultimately beneficial to reduce fat in brains, improving the function of small glial cells and their ability to eat the amyloid blylaid plaques, and improving the signs of nervous health in the animal models of Alzheimer’s disease.

“What we have seen is that when we are targeting the enzyme of the fat industry or either to remove or destroy it, we restore the ability of small glial cells to fight the disease and maintain balance in the brain-which is intended to do.”

“This is an exciting discovery that reveals how the toxic protein plate directly affects how fat is formed and metabolized by microscopic cells in Alzheimer’s brains,” said Berra Prakash, the first participant of the study. “While the latest works in this field focused on the genetic basis of the disease, our research paves the way to understand how to target fats and their paths within the immune cells of the brain to restore their function and combat the disease.”

“It is extremely exciting to link fat metabolism to the immune functional in Alzheimer’s disease,” said Palac Manchnda, the first participant author. “By identifying this fat burden and the DGAT2 key that drives it, we reveal a completely new therapeutic angle: restore metabolism to microorganums and you can restore brain defense against the disease.”

In Bordeaux, Chopra joined the research by Brakash, Manchnda, Kanchehan Bisht, Kushk Sharma, Brighath R. Wigshan, Ketlin Randolph, Matthew Clark, Jonathan Fine, Elizabeth Theire and Chech Chang. Their research was produced with the support of the US Department of Defense and National Institutes of Health.