An analysis of 22 large gene expression datasets pointed to exercise and activity in general as the most effective theoretical treatments for reversing gene expression typical of Alzheimer’s disease. Fluoxetine, a well-known antidepressant, also showed benefits, especially when combined with exercise. Curcumin also showed positive effects. This research scientific report.
Alzheimer’s disease is a complex neurodegenerative disease that affects multiple brain regions. It is the most common disease that causes dementia and is very difficult to treat. During the course of the disease, abnormal clusters of proteins called tau accumulate inside neurons.
Another type of protein aggregates to form so-called amyloid plaques, which collect between neurons and disrupt cell function. These and other changes impair brain function in various areas, leading to brain cell dysfunction and death.
“Alzheimer’s is a devastating disease for individuals, but it also affects families,” said Stephen C. Gammie, professor at the University of Wisconsin-Madison and corresponding author of the new study. .
Alzheimer’s disease is a complex disorder involving the dysregulation of thousands of genes across many brain regions. As with individual cells, specific brain regions have specific gene expression profiles, but there is a general pattern of dysregulation seen throughout the central nervous system in patients with Alzheimer’s disease.
Scientists study gene expression patterns to identify those that are characteristic of particular diseases. One such method is a technique called signature verification. It can also be used to find treatments that reverse patterns of gene expression characteristic of certain diseases. However, there is no guarantee that reversal of disease-associated gene expression patterns will lead to reversal of disease symptoms.
The authors of this study used the aforementioned signature matching technique to identify gene expression patterns typical of Alzheimer’s disease and sought to create a ‘gene expression portrait’ of Alzheimer’s disease. They compared data from Alzheimer’s patients with controls without Alzheimer’s disease. Such studies can mainly be done after a person has died, that is, postmortem.
Therefore, the brain samples of the 22 datasets used in this study were taken from people who died while suffering from Alzheimer’s disease and these were compared with controls.
“Portrait was created to identify consistent alterations in dysregulated Alzheimer’s disease genes across multiple brain regions and multiple studies. and downregulated genes were used, but information from the top 8000 upregulated and downregulated genes was also included. A ranking system was used in which genes and increments from 1,000 to 8,000 were assigned,” explained the study authors.
The results indicated, “The three most dysregulated genes in AD portraits are inositol triphosphate kinase, ITPKB (upregulated), astrocyte-specific intermediate filament protein, GFAP (upregulated), and rho GTPase, RHOQ. (up-regulation)”. Male and female Alzheimer’s disease gene expression portraits were very similar.
When treatments were considered, the authors of the study reported that out of over 250 possible treatments, exercise and activity were commonly identified as theoretical treatments by reversal of specific large-scale gene expression patterns. Researchers have found that exercise reverses the expression patterns of hundreds of Alzheimer’s-related genes.
“Although this is an indirect theoretical study that integrates data from different datasets, it was interesting that exercise emerged as the most theoretical fit for treatment of Alzheimer’s disease. This is consistent with current direct research finding a positive effect of exercise on blood pressure,” Gammie told PsyPost.
Fluoxetine, a well-known antidepressant marketed under names such as Prozac, also scored well as a therapeutic agent. Researchers reported that fluoxetine, in combination with exercise, reversed 549 Alzheimer’s disease genes. Another positive therapeutic substance was curcumin.
“We were surprised that both exercise and fluoxetine worked so well,” Gammy said. “We also found that a theoretical combination of the two could be useful. , consistent with studies by several groups currently testing the effects of combining the two treatments.”
This study makes an important contribution to our knowledge of the genetics of Alzheimer’s disease and possible treatments through gene reversal. However, the data were obtained from postmortem samples, and reversal of gene expression in the case of diseases such as Alzheimer’s disease does not necessarily mean that the disease course associated with a particular gene expression portrait is similarly reversed. It should be noted that
“One caveat is that we are looking for therapies that reverse Alzheimer’s disease gene expression patterns on a large scale, but only a few specific genes may need to be reversed.” “If so, we need to improve how we score treatments.”
“Also, some patterns of Alzheimer’s disease may be occurring because the brain is trying to fight it, and we don’t want treatments that interfere with these protective efforts.” , may provide insight into how a treatment works or how to uncover potential new treatments, but it is theoretical and only directly addressable to efficacy only scientific research.”
Paper “Large-scale gene expression portrait of Alzheimer’s disease identifies exercise as best theoretical treatment‘ was written by Mason A. Hill and Stephen C. Gammie.
