Placenta-Derived Nasal Spray Shows Promise Against Alzheimer's in Mouse Study

Alzheimer's disease has long been understood as a problem of sticky proteins—amyloid-beta and tau accumulating in the brain and choking off neural function. But researchers increasingly recognize that the disease is more complicated than protein buildup alone. The brain's own immune cells, when chronically activated, can turn destructive. Microglia and astrocytes, meant to protect neurons, instead trigger inflammation that damages the very cells they're supposed to defend. A team of scientists at the Catholic University of the Sacred Heart in Italy wondered whether they could interrupt that inflammatory cascade using an unlikely source: the human placenta.

The researchers extracted tiny particles called extracellular vesicles from cells in the placental amniotic membrane. These nanoparticles, known as hAMSC-EVs, act as messengers between cells, carrying anti-inflammatory and neuroprotective molecules. The team formulated them into a nasal spray—a delivery method that allows the particles to reach the brain directly. They then tested the spray on transgenic mice engineered to develop Alzheimer's-like symptoms. Starting at three months of age, before any cognitive decline appeared, the mice received two doses per week for six months, continuing until they reached nine months old.

The results, published in Translational Neurodegeneration, were striking. Fluorescent dye tracking confirmed that the placenta-derived vesicles penetrated all regions of the hippocampus, the brain's memory center, and made contact with both neurons and microglia. When the researchers put the treated mice through behavioral tests, the animals showed measurably better performance on tasks measuring object recognition and spatial memory compared to untreated controls. The treatment also significantly reduced amyloid-beta deposits in the hippocampus, though it did not alter tau phosphorylation. More importantly, the treated mice exhibited substantially lower signs of neuroinflammation—both astrocytes and microglia showed reduced activation—and their brains contained higher levels of proteins associated with neuroplasticity and synaptic health, including ARC, GluA1, and BDNF.

To test whether the mechanism might work in human cells, the researchers took skin cells from people with sporadic Alzheimer's disease, reprogrammed them into stem cells, and then differentiated them into neurons. When they exposed these human-derived neurons to the EV treatment in the lab, the cells showed reduced deterioration and restored healthier expression of neuroplasticity-related proteins. The findings align with earlier work by some of the same team suggesting that placental mesenchymal stromal cells possess powerful immune-modulating properties that could be harnessed for regenerative medicine.

The mechanism appears to work not through brute immunosuppression but through reshaping the brain's inflammatory environment itself. By altering the behavior of microglia, shifting the balance of inflammatory molecules called cytokines, and promoting factors that support neuronal integrity and synaptic function, the vesicles seem to create conditions where the brain can maintain its own health. Senior researcher Claudio Grassi emphasized that these are preclinical findings—results in mice and lab-grown human cells—and do not yet constitute a therapy ready for patients. The next critical step is determining whether the same protective effects would emerge in humans with actual cognitive decline. The researchers plan further studies to validate the approach in human subjects and to map out the precise molecular pathways through which placental biology might defend against neurodegeneration. If those studies succeed, the placenta could become an unexpected ally in the long fight against Alzheimer's.