Placenta-Derived Nasal Spray Slows Alzheimer's Progression

What if the placenta — an organ we think of only at birth — could be repurposed to protect the aging brain? That provocative idea is the starting point for a new preclinical study coming out of Italy, where researchers used tiny particles harvested from the placental amniotic membrane to treat Alzheimer's-like disease in mice.

The team, led by cell biologist Andrea Papait at the Catholic University of the Sacred Heart and published in Translational Neurodegeneration, isolated extracellular vesicles from amniotic mesenchymal stromal cells (hAMSC-EVs). These nanoscale messengers shuttle proteins and genetic material between cells and have been explored for regenerative medicine because of their anti-inflammatory and neuroprotective potential.

Mice engineered to develop Alzheimer’s features received the vesicle-laden nasal spray twice weekly for six months, beginning before symptoms appeared. Why the nose? Intranasal delivery can bypass barriers that block many drugs from reaching the brain. Here it worked: fluorescent tracing showed the vesicles distributed throughout the hippocampus and were taken up by both neurons and microglia.

Behavior changed. Mice treated with the placental EV formulation performed better on object-recognition and spatial-memory tests than untreated controls. Under the microscope, treated brains had fewer amyloid-beta deposits in the hippocampus, although abnormal tau phosphorylation appeared unchanged. At the same time, cellular signs of neuroinflammation dropped — astrocytes and microglia were less reactive — and markers tied to synaptic plasticity, including ARC, GluA1 and BDNF, rose.

In short, intranasal placenta-derived vesicles reduced amyloid burden and calmed neuroinflammation while boosting proteins linked to synaptic health.

The team did not stop at mice. In a lab dish they reprogrammed skin cells from people with sporadic Alzheimer’s into neurons. Those human-derived neurons exposed to the EVs showed less degeneration and a partial restoration of neuroplasticity-related proteins, suggesting the effect is not limited to a single animal model.

Mechanistically, the data point toward modulation rather than blanket suppression of immunity. The authors argue the vesicles reshape the inflammatory microenvironment — nudging microglia toward a less damaging phenotype and altering cytokine profiles in a way that supports neuronal integrity and synaptic function.

There is a cautious note. These are preclinical findings, and the jump from mice and cultured human neurons to an effective human therapy is large. Senior researcher Claudio Grassi emphasizes that this work "points to a promising direction" but does not yet deliver a treatment for people living with Alzheimer’s.

Still, the study adds to a growing body of evidence that mesenchymal stromal cell derivatives from the placenta have potent immune-modulating properties and may be worth exploring further for neurodegenerative disease. If future studies can pin down the molecular signals at play and demonstrate safety and efficacy in people, intranasal extracellular vesicles could open a novel route for addressing neuroinflammation in Alzheimer's and beyond.

For now, the placenta has stepped out of the delivery room and into the lab as an unexpected ally in the fight against cognitive decline — and the next chapters will determine whether that ally can help patients as well as rodents.