Researchers Leverage AI to Decode Alzheimer’s Disease and Uncover Promising Drug Targets

Alzheimer’s disease is a critical neurological disorder that affects millions of people across the United States. It impacts the behavior, thinking, and memory, of those affected. In recent times, drugs can treat symptoms, but discovering a cure has been difficult, largely because the etiology of Alzheimer’s illness is unknown.

According to Alzheimer’s Association, more than 6 million Americans have Alzheimer’s disease. And unfortunately, this figure is expected to increase to around 13 million by 2050. It’s hard to imagine how people and their loved ones deal with this. But here’s the good news: scientists and researchers are going all-in with the help of artificial intelligence (AI) to find a cure for the disease.

With the use of AI systems, researchers can quickly identify potential drug targets, accelerating the search for potent cures. Despite decades of genetic research on late-onset Alzheimer’s disease, the molecular pathways underlying the disease remain unknown.

Recently, researchers from the University of Arizona College of Medicine-Tucson and Harvard University teamed up to identify drug targets for Alzheimer’s disease cure. The team used artificial intelligence to discover the causes of Alzheimer’s disease and the potential therapeutic targets. In this article, let’s explore the works of Rui Chang, associate professor of neurology, and his team. The research was published in Nature Journal.

What is Alzheimer’s Disease?

Alzheimer’s disease is a debilitating neurodegenerative disorder. According to Harvard-trained neuroscientist Shaun Patel, Ph.D., neuroinflammation begins in the brain and extends throughout it, affecting neuronal pathways that support cognitive abilities.

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Symptoms of Alzheimer’s Disease

• Memory challenges: Forgetting someone’s name is a common symptom of natural, age-related cognitive decline. More frequent, substantial, and recurrent memory impairments, on the other hand, may be an early indication of Alzheimer’s or a different kind of dementia.
• Struggle to perform basic activities: Making errors while conducting routine chores such as washing, dressing, and performing typical everyday duties such as drafting grocery lists or managing one’s money may also be an early warning sign of Alzheimer’s disease. Another classic example is having difficulty driving to a known destination, forgetting exactly where someone is going and how to get there while en route.
• Meek decision-making abilities: Executive dysfunction errors can be a sign of the neurological damage brought on by Alzheimer’s disease. Executive function is a series of high-level cognitive functions that regulate behaviors and activities. While making mistakes is an inevitable aspect of human life, people with Alzheimer’s disease may have more severe alterations in judgment or decision-making skills.

How the Research Team is Using AI 

Researchers at the University Of Arizona College Of Medicine collaborated with Harvard University to find the causes of the disease. They used artificial intelligence to follow the process from a healthy brain cell to one affected by Alzheimer’s disease.

Determining the Changes in the Body 

While explaining the series of events that take place in cells resulting in the changes in the body, Chang, stated that the process involved different pathways. He further stated that this is the first study to show that using AI and big data to find treatments for Alzheimer’s disease by targeting novel pathways or combinations of pathways.

Chang’s AI system extracted information about genetic and biological processes using tissue samples from over 2,000 Alzheimer’s disease-affected brains obtained from a national database, creating a computerized network model of the human brain.

“Amyloid plaques and tau tangles are downstream effects of a series of genetic mutations in upstream pathways that induce Alzheimer’s disease. It’s very doubtful that targeting these abnormal structures directly will be effective.”

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It indicated that drugs that were responsible for stopping the production of plaques and tangles failed the clinical trials. This means that they are not causing Alzheimer’s disease, but they are more likely a result of earlier events.

According to Chang, The correct approach is to attack the disease upstream, particularly by hitting several targets at once. Since Chang employs AI to map this landscape, it is crucial to comprehend the entire environment. The use of artificial intelligence (AI) is a cutting-edge technology that can dissect vast amounts of data into a network model to get a comprehensive picture of all upstream activities and reveal which upstream genes coordinately control significant downstream genes.

Changes Discovered by AI

Chang employed artificial intelligence to find 19 particularly intriguing genomic regions unique to neurons that appear to move neurons closer to a disease state. By utilizing stem cells to grow neurons in Petri dishes and testing what would happen when the genes were turned off, study collaborators at Harvard confirmed the significance of these genes in the onset of Alzheimer’s disease.

They discovered that ten of these genes had an impact on the formation of tangles and plaques and may be used as targets for Alzheimer’s disease treatments.

“If deactivating these genes significantly changes the levels of amyloid plaques and tau tangles, then this is a validated target to develop treatments for Alzheimer’s disease.”

3D Models to Discover if Existing Drugs Fit into the Targets

After successfully identifying the gene target, the next step is to look for specific drugs that will hit the target. Chang used 3D computer models to test if already available chemicals and medications might fit into potential therapeutic targets similarly to how a lock and key do.

Chang explained that the process will considerably speed up the development and discovery of new drugs because 6,000 targets are being studied simultaneously rather than just one gene at a time.

Virtual Screening 

The scientists electronically tested millions of small-molecule compounds and natural products that the Food and Medication Administration had approved against more than 6,000 targets before settling on roughly 3,000 medication candidates.

The team has received funding from the National Institutes of Health funding authorizing clinical trials on three of the compounds, along with numerous tiny molecules they are researching further. They anticipate starting human trials soon.

Conclusion 

It’s a difficult journey for people suffering from Alzheimer’s disease. The disease impacts not just the person, who has been afflicted, but also their loved ones’ families and other close relationships. But this remarkable discovery by the researchers at the University of Arizona College of Medicine-Tucson and Harvard University provides more hope and quicker progress for Alzheimer’s patients and their families everywhere. With a possible cure, the emotional pain, grief, and helplessness brought on by seeing a loved one deteriorate would be lessened if there was a solution.

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