Scientists at Johns Hopkins Medicine revealed on July 22, 2026, new evidence that small clusters of brain tissue, grown from cells from individuals with Alzheimer’s, can help predict how different patients respond to medications. The drugs in question are used to control psychiatric symptoms often associated with the disease.
The investigation focused on laboratory-grown brain tissue, known as organoids. The findings reinforce the growing realization that these scaled-down brain models have the potential to assist researchers in developing and selecting more targeted therapies for specific groups of people affected by Alzheimer’s, the most common form of dementia, which affects more than 7 million Americans. This study is crucial because it points to a future where Alzheimer’s therapy will not be a single approach, but rather adapted to each patient’s individual biology, optimizing results and minimizing adverse effects.
The team also identified that the organoids release small particles, called extracellular vesicles, which carry cellular information. Such particles may, in the future, offer new biomarkers for diagnosing Alzheimer’s and determining the stage of disease progression.
The study, which received partial funding from the National Institutes of Health (NIH), was published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Mini brain models can help with personalized care
“Our study suggests that large-scale, patient-derived brain organoids and the vesicles they release can help us stage Alzheimer’s disease, investigate the mechanisms that drive it, and evaluate how subgroups of patients may respond to different treatments,” says study leader Vasiliki Machairaki, Ph.D., associate professor of genetic medicine at Johns Hopkins University School of Medicine.
There is currently no cure for Alzheimer’s. However, selective serotonin reuptake inhibitors (SSRIs) are often prescribed to control neuropsychiatric symptoms, such as anxiety, depression, and agitation, which affect almost all patients. Responses to these medications, however, vary considerably, explains Machairaki.
Johns Hopkins researchers examined miniature models of the hindbrain, an area at the back of the skull that controls vital functions such as breathing, sleep and heart rate. The team’s goal was to see if these models could reveal molecular signals that would indicate whether escitalopram oxalate, an SSRI antidepressant, would help reduce symptoms linked to Alzheimer’s.
Transforming patients’ blood cells into brain tissue
The scientists began the work with blood samples collected, with permission, from individuals with Alzheimer’s disease at the Johns Hopkins Alzheimer’s Disease Research Center, which is funded by the NIH.
They then reprogrammed the blood cells to return to a stem cell-like state. These cells, known as induced pluripotent stem cells, have the ability to develop into any type of cell in the body.
Using induced pluripotent stem cells from both people with Alzheimer’s and healthy individuals, the Johns Hopkins team created hindbrain organoids. These organoids contained neurons, the specialized brain cells responsible for producing the neurotransmitter serotonin.
The cells were induced to organize themselves into small, pea-sized clumps of brain tissue that resemble the hindbrain. The study encompassed hundreds of organoids, representing individual Alzheimer’s patients and healthy participants. Machairaki believes this could be one of the largest brain organoid studies ever carried out in the field of Alzheimer’s.
Alzheimer’s organoids present distinct molecular alterations
Patient-derived organoids reproduced several crucial biological features of Alzheimer’s disease at the molecular level.
Compared to organoids created from healthy individuals, those cultured with cells from people with Alzheimer’s showed disparities in proteins involved in brain intercellular communication, inflammation and pathways associated with the disease.
The researchers later treated the organoids with escitalopram oxalate, a widely prescribed antidepressant.
In some organoids derived from patients, the medication amplified proteins that act in serotonin signaling and communication between brain cells. These are precisely the pathways that antidepressants seek to influence. Other organoids showed little or no molecular response.
“We use these organoids to model how tissue from some patients might respond to a commonly prescribed SSRI,” explains Machairaki. “On a larger scale, our model could be used in the future to identify subgroups of patients, based on underlying molecular mechanisms, who are more likely to respond to certain drugs and thus help us create precise, targeted long-term treatments.”
Tiny vesicles may reveal drug response
In a next step, the team investigated whether the extracellular vesicles released by the organoids could act as biomarkers for Alzheimer’s disease or help researchers assess the tissue’s response to treatment.
Before and after treating the organoids with escitalopram, the scientists analyzed the proteins present in extracellular vesicles released from both patient-derived organoids and healthy control organoids.
The vesicles contained proteins essential for crucial brain activities, including communication between neurons, memory and the release of neurotransmitters.
Organoids cultured from cells from individuals with Alzheimer’s showed clear changes in several proteins associated with the disease. Levels of RAB3A, NSF and ATCAY were reduced in Alzheimer’s organoids. These proteins play important roles in normal signaling between brain cells.
After administration of escitalopram, the levels of some proteins increased in certain samples. The changes were particularly notable in proteins related to serotonin signaling and the synaptic pathways that antidepressants target.
Some organoids demonstrated significant molecular responses, while others showed little or no change. According to Machairaki, this variation suggests the possibility that extracellular vesicles from cerebral organoids could eventually help identify patients most likely to benefit from a specific treatment.
Building more realistic brain organoids
Machairaki plans to develop even more advanced organoids, which will include immune cells and blood vessel-like networks. Incorporating these features could make tissues more similar to living human brain tissue.
With further investigation, she hopes that the extracellular vesicles could one day function as a kind of liquid biopsy. This test could potentially help diagnose Alzheimer’s, determine its stage and identify the specific subtype of the disease in each patient.
Machairaki highlighted that the current study represents a significant first step towards this goal.
