Research reveals the best potential way to treat Alzheimer’s

A new study conducted by researchers from the University of Wisconsin-Madison worked on Alzheimer's Disease (AD) large-scale genetic datasets to detect its genetic patterns across the brain and used them to identify treatment methods that could reverse the AD patterns.

The results have shown that out of over 250 potential alternatives, exercise is the most effective theoretical treatment for AD.

"Exercise reversed expression patterns of hundreds of AD genes across multiple categories, including cytoskeleton, blood vessel development, mitochondrion, and interferon-stimulated related genes," wrote the scientists in the study paper, which was published in the journal Scientific Reports on October 13, 2022.

A disease with no current treatment

Alzheimer's is the most common type of dementia among older adults. Mostly showing its first symptoms at the age of 60s, it slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks.

There is no cure for AD, yet. However, medications are employed to temporarily improve or slow down the progression of symptoms.

In search of potential treatment models, the new research analyzed 250 potential treatment datasets in humans and rodents and identified the most effective theoretical treatments for reversing AD gene expression patterns.

Exercise turned out to be among the top three therapies that might reverse AD. However, the authors also underlined that majority of trials were performed on rodents. "The potential ability of exercise to reverse AD patterns was striking," noted the authors in the study.

The research team also stated that when combined with exercise, a selective serotonin reuptake inhibitor (SSRI) antidepressant named Fluoxetine has shown positive results by reversing 549 AD genes.

Identifying what could worsen Alzheimer's

The method of scoring and ranking also helped the research team identify what could worsen AD. The top two datasets were from human CNS tissue and linked to alcohol, indicating that alcohol abuse may be a risk factor for AD.

The study authors stated that the examined treatments should be viewed as theoretical for now since treatment expression studies varied widely across multiple factors, such as sex, species, treatment length, etc. While research demonstrates that exercise aids in preventing the onset and progression of AD, further human studies should be conducted to find out how exercise reverses AD.

Abstract:

Alzheimer’s disease (AD) is a complex neurodegenerative disorder that affects multiple brain regions and is difficult to treat. In this study we used 22 AD large-scale gene expression datasets to identify a consistent underlying portrait of AD gene expression across multiple brain regions. Then we used the portrait as a platform for identifying treatments that could reverse AD dysregulated expression patterns. Enrichment of dysregulated AD genes included multiple processes, ranging from cell adhesion to CNS development. The three most dysregulated genes in the AD portrait were the inositol trisphosphate kinase, ITPKB (upregulated), the astrocyte specific intermediate filament protein, GFAP (upregulated), and the rho GTPase, RHOQ (upregulated). 41 of the top AD dysregulated genes were also identified in a recent human AD GWAS study, including PNOC, C4B, and BCL11A. 42 transcription factors were identified that were both dysregulated in AD and that in turn affect expression of other AD dysregulated genes. Male and female AD portraits were highly congruent. Out of over 250 treatments, three datasets for exercise or activity were identified as the top three theoretical treatments for AD via reversal of large-scale gene expression patterns. Exercise reversed expression patterns of hundreds of AD genes across multiple categories, including cytoskeleton, blood vessel development, mitochondrion, and interferon-stimulated related genes. Exercise also ranked as the best treatment across a majority of individual region-specific AD datasets and meta-analysis AD datasets. Fluoxetine also scored well and a theoretical combination of fluoxetine and exercise reversed 549 AD genes. Other positive treatments included curcumin. Comparisons of the AD portrait to a recent depression portrait revealed a high congruence of downregulated genes in both. Together, the AD portrait provides a new platform for understanding AD and identifying potential treatments for AD.