Alzheimer’s disease is the most common form of dementia and affects millions of people worldwide. It slowly destroys memory, thinking, and the ability to carry out everyday activities.
Although scientists have developed medicines that can ease some symptoms, there is still no cure, and one of the biggest challenges is that treatments do not work equally well for everyone.
Researchers at Johns Hopkins Medicine have now taken an important step toward solving this problem. Their study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, suggests that tiny pieces of brain tissue grown from a patient’s own cells could help predict which medicines may work best for that individual.
These tiny brain tissues are known as organoids. They are not complete brains and cannot think or feel. Instead, they are small collections of human brain cells grown in the laboratory that copy some of the structure and activity of real brain tissue. Scientists use them to study diseases that cannot easily be examined inside the living human brain.
To build the organoids, the team collected blood samples from people with Alzheimer’s disease and healthy volunteers. The blood cells were reprogrammed into stem-cell-like cells that can develop into many different types of human tissue. The researchers then guided these cells to form pea-sized pieces of hindbrain tissue containing serotonin-producing nerve cells.
The hindbrain helps control important functions such as breathing, sleep, and heart rate. Although Alzheimer’s mainly affects memory-related brain regions, studying the hindbrain allowed researchers to investigate serotonin pathways that are linked with depression, anxiety, and agitation, symptoms that are common in Alzheimer’s disease.
Doctors often prescribe antidepressants called selective serotonin reuptake inhibitors, or SSRIs, to reduce these symptoms. One commonly used medicine is escitalopram. However, some patients improve while others experience little benefit, and doctors currently have no reliable way to predict the response before treatment begins.
When the scientists treated hundreds of organoids with escitalopram, they found clear differences. Some organoids showed stronger activity in serotonin pathways and proteins involved in communication between nerve cells, while others showed little change.
These differences closely matched the idea that patients may naturally belong to different biological subgroups.
The researchers also discovered that the organoids released microscopic particles called extracellular vesicles. These tiny packages carry proteins and other molecules that reflect what is happening inside cells. Organoids from people with Alzheimer’s contained different protein patterns from those grown from healthy volunteers.
The protein changes also shifted after treatment in some organoids, suggesting that these tiny vesicles might one day act as simple biological markers to monitor disease progression or predict how well a patient will respond to medication without needing invasive testing.
Review and analysis: This study is an important step toward personalized medicine for Alzheimer’s disease. The research shows that patient-derived brain organoids may help explain why some people respond to medicines while others do not.
However, the work was performed in laboratory-grown tissue rather than living patients, so much more research and clinical testing are needed before the approach can be used in hospitals.
If future studies confirm these findings, brain organoids and extracellular vesicles could become valuable tools for selecting treatments, diagnosing disease earlier, and monitoring disease progression.
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Source: Johns Hopkins Medicine.
