An analysis of 22 large-scale gene expression datasets showed exercise and general activity to be the most effective theoretical treatment for reversing gene expressions typical of Alzheimer’s disease. Fluoxetine, a well-known antidepressant, has also shown an effect, especially when combined with exercise. Curcumin has also shown positive effects. The study was published in Scientific reports.
Alzheimer’s disease is a complex neurodegenerative disease that affects several regions of the brain. It is the most common disease that causes dementia and is very difficult to treat. During disease, abnormal collections of proteins called tau build up inside neurons.
Another type of protein clumps together to form so-called amyloid plaques that accumulate between neurons and disrupt cellular functions. These and other changes impair brain function in different regions and lead to brain cell dysfunction and death.
“Alzheimer’s disease is a devastating disease for individuals, but it also has a negative impact on family members. We were interested in exploring the basis of the disease and possible treatments,” said Stephen C. Gammie, a professor at the University of Wisconsin-Madison and corresponding author of the new study.
Alzheimer’s disease is a complex disease that involves dysregulated expression of thousands of genes in many regions of the brain. Although specific brain regions have specific gene expression profiles, as is also the case with individual cells, there are common patterns of dysregulation that are found in the central nervous system in patients with AD. Alzheimer’s.
Scientists study gene expression patterns to identify those that are characteristic of a particular disease. One of the ways to achieve this is a technique called signature matching. It can also be used to find treatments that can reverse gene expression patterns characteristic of a particular disorder. There is, however, no guarantee that a reversal of disease-related gene expression patterns will lead to the reversal of disease symptoms.
The authors of this study used the signature-matching technique mentioned in an attempt to identify gene expression patterns typical of Alzheimer’s disease, in order to create a “gene expression portrait” of Alzheimer’s disease. Alzheimers. They compared data from people with the disease to controls, people without Alzheimer’s disease. Studies like this can mostly be done after a person dies, i.e. post mortem.
Therefore, brain samples in the 22 datasets used in the study were taken from people who died while suffering from Alzheimer’s disease and these were compared to controls – samples from brains of people who died without Alzheimer’s disease.
“The portrait was done to identify consistent changes in dysregulated Alzheimer’s disease genes across multiple brain regions across multiple studies. To do this, a scoring system was used that highlighted the top 1000 up-regulated and down-regulated genes from each study, but also included information from the top 8000 up-regulated and down-regulated genes. on the decline. In short, a ranking system was used in which genes in the top 1,000 and increments of 1,000 to 8,000 were assigned a decreasing value,” the study authors explained.
The results showed that “the three most dysregulated genes in the AD portrait were inositol trisphosphate kinase, ITPKB (upregulated), astrocyte-specific intermediate filament protein, GFAP (upregulated), and rho GTPase, RHOQ (positively regulated)”. The Alzheimer’s disease gene expression portraits for men and women were very similar.
When treatments were considered, the study authors report that of over 250 possible treatments considered, exercise and general activity were identified as the theoretical best treatment via reversal of certain expression patterns. gene on a large scale. The researchers found that exercise reversed the expression patterns of hundreds of genes linked to Alzheimer’s disease.
“Although this is an indirect, theoretical study that merges data from disparate data sets, it was interesting to note that exercise emerged as the best theoretical match for the treatment of Alzheimer’s disease. This finding is consistent with current direct studies that find positive effects of exercise on cognition,” Gammie told PsyPost.
Fluoxetine, a well-known antidepressant sold commercially under names such as Prozac, also scored well as a treatment. In combination with exercise, researchers report that fluoxetine reversed 549 Alzheimer’s disease genes. Another positive therapeutic substance was curcumin.
“We were surprised that exercise and fluoxetine worked so well,” Gammie said. “We also found that a theoretical combination of the two could be helpful and this is consistent with studies from some groups now combining the two treatments and testing the effects.”
The study makes an important contribution to the knowledge of the genetics of Alzheimer’s disease and possible treatments by gene inversion. It should be noted, however, that the data come from post-mortem samples and that the inversion of gene expression in the case of diseases such as Alzheimer’s disease does not necessarily mean that the course of the disease associated with a certain gene expression portrait will also reverse.
“A caveat is that we are looking for treatments that reverse gene expression patterns in Alzheimer’s disease on a large scale, but it’s possible that only a small number of specific genes need to be reversed,” Gammie explained. “If that’s the case, we would need to refine how we assess treatments.”
“Furthermore, it is possible that certain AD patterns occur because the brain is trying to fight off Alzheimer’s disease and one would not want treatments that interfere with these protective efforts. Finally, this approach can provide information about how treatments would work or highlight potential new treatments, but it is theoretical and only direct studies can address the effectiveness of treatments.
The article “The large-scale gene expression portrait of Alzheimer’s disease identifies exercise as the best theoretical treatment” was written by Mason A. Hill and Stephen C. Gammie.
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