Potential ability of exercise to reverse Alzheimer’s striking, finds new US study

Scientists from University of Wisconsin-Madison, also identified the selective serotonin reuptake inhibitor antidepressant Fluoxetine as being helpful, especially when combined with exercise.

Representational image | Pixabay

Bengaluru: Scientists from the University of Wisconsin-Madison, USA, have studied large-scale genetic datasets to identify Alzheimer’s Disease (AD) genetic patterns across the brain. They then identified treatments that could theoretically reverse AD patterns, and zeroed in on exercise as the most practical and beneficial treatment out of 250 potential remedies.

Exercise proved beneficial in reversing several accompanying conditions as well, found the study.

“Exercise reversed expression patterns of hundreds of AD genes across multiple categories, including cytoskeleton (protein structure inside cells), blood vessel development, mitochondrion, and interferon-stimulated ( immune-system-related-signalling) related genes. Exercise also ranked as the best treatment across a majority of individual region-specific AD datasets and meta-analysis AD datasets,” write the authors in the paper.

Comparing the AD portrait, or patterns of genetic expressions from large datasets, with depression portraits, showed overlapping downregulation or reduction in quantity of relevant genes.

Along with exercise, the authors also identified the selective serotonin reuptake inhibitor (SSRI) antidepressant Fluoxetine as being helpful, especially when combined with exercise. Curcumin, the yellow pigment that is primarily found in turmeric, also was in the top three best treatments following the previous two.

The findings were published in the journal Nature.

AD is the most-common cause for dementia and can lead to the formation of neurofibrillary tangles of tau proteins (called tau tangles) in brain cells making them physically weak, causes dysregulated or impaired expression of genes across various regions of the brain, and is extremely difficult to treat. Many large-scale genetic maps or gene expression studies in both post-mortem and control (non-diseased) brains show similar gene alterations across about 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 gene expression portrait of AD. This portrait, or genetic map, captures repeated patterns of impaired/dystregulated gene expressions across the brain. They also recorded that these brain patterns were consistent in men and women.

Exercise best-performing theoretical treatment

The researchers further analysed 250 potential treatment datasets for various drugs for the central nervous system in humans and rodents. This included potential treatment for AD as well. Using this, they identified the top theoretical treatments for reversing AD dysregulated gene expression patterns.

For the AD portrait, the top three scoring treatments for reversing Alzheimer’s without exacerbating it were exercise in various datasets. However, the authors clarify that most studies had been done on rodents.

Among the top five treatments were three datasets with exercise, followed by the antidepressant fluoxetine, and the plant pigment curcumin. While the antidepressant helped with depression too, curcumin has not been fully investigated in any studies and showed potential for negative effects in the hippocampus region of the brain.

The 6th highest treatment was safflower oil in a high-fat diet (when compared with flaxseed oil alone), while the stimulant cocaine had three matches in the top 25 treatments datasets as well.

Exercise ranked as the best-performing theoretical 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 striking,” described the authors in the study. With exercise, in the first and second-ranked treatments, 409 and 344 AD genes were reversed. This included cell adhesion, cytoskeletal binding, neuron projection (physical growing of neurons), improving 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 reversed while also improving cognition.

The analysis further allowed the researchers to identify potential problematic treatments that may exacerbate AD gene expression patterns, including alcohol abuse.

The authors clarified in their study that the treatments should be viewed as theoretical currently, as the original datasets used in the study — derived from other studies — were not built to explicitly examine the role of exercise in reversing AD. While studies have consistently shown that exercise helps in preventing the onset or development of AD, further human studies are needed to examine the precise way that exercise works to reverse AD.

(Edited by Poulomi Banerjee)