New Delhi: Scientists at Johns Hopkins Medicine have found a way to create ‘mini-brains’ using cells from patients with Alzheimer’s disease. This allows them to better understand how the disease impacts different regions of the brain, and how patients might respond to medication.
The study, which received partial funding from the National Institutes of Health, was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“Our study suggests that large-scale, patient-derived brain organoids (mini brains) and the vesicles they secrete can help us stage Alzheimer’s disease, investigate the mechanisms that drive it and assess how patient subgroups may respond to different treatments,” Vasiliki Machairaki, Ph.D, associate professor of genetic medicine at the Johns Hopkins University School of Medicine, said in a statement.
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A mysterious disease
At present, there is no cure for Alzheimer’s. It is one of the most prevalent forms of dementia and affects over 55 million people globally according to the World Health Organisation. The WHO recognises the disease as the seventh leading cause of death with nearly 10 million new cases emerging every year. What makes the disease particularly tricky to address medically is that it is linked to over 90 genetic risk regions in the brain.
Patients often develop different types of symptoms and do not respond in a uniform manner to treatments. Results from studies on animals are also unreliable because they cannot factor in how the disease varies from person to person.
To address this, researchers collected blood cells from patients and reprogrammed them into stem cells which were then grown into 3D ‘mini brains’, also known as brain organoids, that mimic parts of the human brain. In particular, scientists recreated parts of the brain where they would be able to observe how serotonin producing neurons are affected by the disease since the early onset of Alzheimer’s is linked to depression and anxiety.
Within these brains scientists observed extracellular vesicles (EVs) which are tiny particles released by cells that carry proteins and molecules which suggest what might be going on within that call. EVs from the brain enter the blood flow and prove to be bio-markers of how a disease is impacting a cell.
By studying both the mini brains and the EVs released by them, scientists could observe what was happening inside brain cells and the kind of molecular signals they were emitting.
Scientists found that the mini brains were quite accurate in depicting how Alzheimer’s actually affects a patient. The EVs revealed that there were about 28 proteins which were significantly altered by Alzheimer’s. Many of these proteins could be targets for medical interventions. The EVs themselves could someday allow Alzheimer’s to be diagnosed based on blood tests alone.
However, these findings are still part of a small laboratory model using only 30 people. The findings still have to be validated by bigger patient cohorts. Researchers are also yet to prove that EV biomarkers would indeed appear on routine blood tests.