Bengaluru: Scientists at the University of Wisconsin-Madison, USA, have studied large-scale genetic data sets to identify genetic patterns of Alzheimer’s disease (AD) throughout the brain. They then identified treatments that could theoretically reverse AD patterns and zeroed in on exercise as the most practical and beneficial treatment of 250 potential remedies.
Exercise was also shown to be beneficial in reversing several accompanying conditions, the study found.
“Exercise inverted expression patterns of hundreds of AD genes in multiple categories, including the cytoskeleton (protein structure within cells), developing blood vessels, mitochondria, and genes related to interferon stimulation (signaling related to the immune system). Exercise also ranked as the best treatment in most region-specific AD datasets and meta-analysis AD datasets,” the authors write in the article.
Comparison of the AD portrait, or patterns of gene expressions from large data sets, with depression portraits, showed an overlapping downregulation or reduction in the number of relevant genes.
Along with exercise, the authors also found the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine to be helpful, especially when combined with exercise. Curcumin, the yellow pigment found primarily in turmeric, was also in the top three treatments after the previous two.
The findings were published In the diary Nature.
AD is the more common cause of dementia and can lead to the formation of neurofibrillary tangles of tau proteins (called tau tangles) in brain cells, which weakens them physically, causes dysregulated or impaired expression of genes in various brain regions, and is extremely difficult to treat. Many large-scale genetic mapping or gene expression studies in postmortem and control (non-diseased) brains show similar genetic alterations in approximately 20,000 protein-coding genes associated with AD.
The authors used 22 datasets derived from 67 public human AD gene expression datasets to create a portrait of AD gene expression. This portrait, or genetic map, captures repeated patterns of impaired/dysregulated gene expression throughout the brain. They also found that these brain patterns were consistent in men and women.
also read: It’s World Alzheimer’s Day: what you should know about the disease that damages the brain
Exercise theoretical treatment of better performance
The researchers further analyzed 250 datasets of potential treatments for various central nervous system drugs in humans and rodents. This also included the potential treatment for AD. Using this, they identified the best theoretical treatments to reverse the dysregulated gene expression patterns of AD.
For the AD portrait, the three highest-scoring treatments for reversing Alzheimer’s without exacerbating it were exercise across multiple data sets. However, the authors clarify that most of the studies had been carried out in rodents.
Among the top five treatments were three data sets with exercise, followed by the antidepressant fluoxetine and the plant pigment curcumin. While the antidepressant also helped with depression, curcumin has not been fully investigated in any studies and showed potential for negative effects on the hippocampal region of the brain.
The sixth highest treatment was safflower oil in a high-fat diet (compared to flaxseed oil alone), while the stimulant cocaine also had three matches in the top 25 treatment data sets.
Exercise ranked as the theoretical best-performing treatment, along with exercise combined with other treatments, in both male and female AD portraits.
“The potential ability of exercise to reverse AD patterns was surprising,” the authors described in the study. With exercise, in the first and second ranked treatments, 409 and 344 AD genes were reversed. This included cell adhesion, attachment to the cytoskeleton, neuronal projection (physical growth of neurons), enhancement of blood vessels and their development, as well as that of the circulatory system. AD is also associated with decreased blood flow to the brain, something that exercise reverses while improving cognition.
The analysis also allowed the researchers to identify potentially problematic treatments that may exacerbate gene expression patterns of AD, including alcohol abuse.
The authors clarified in their study that the treatments should be viewed as theoretical at present, as the original data sets used in the study, derived from other studies, were not created to explicitly examine the role of exercise in AD reversal. Although studies have consistently shown that exercise helps To prevent the onset or development of AD, more human studies are needed to examine precisely how exercise works to reverse AD.
(Edited by Poulomi Banerjee)
also read: US approves Alzheimer’s drug for the first time in 20 years. What is it and why is it controversial?
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