Placenta-Derived Nasal Spray Shows Promise Against Alzheimer’s Disease

Experimental Treatment Calms Brain Inflammation, Improves Memory In Mice

A nasal spray made from placenta stem cells cut harmful amyloid buildup by more than half in the brains of Alzheimer’s mice and improved their memory performance, according to a new study from Italian researchers. The same treatment also protected human brain cells grown from Alzheimer’s patients’ own skin samples, offering two separate layers of evidence for an approach that could reshape how the disease is treated.

Behind the spray are tiny fluid-filled packets called extracellular vesicles, naturally released by stem cells from the amniotic membrane of human placentas. These packets act like tiny messengers, carrying genetic instructions and proteins that communicate with other cells. When researchers sprayed them into the noses of mice bred to develop Alzheimer’s-like brain changes, the packets traveled to the hippocampus, the brain region most responsible for memory, where both neurons and the brain’s resident immune cells absorbed them.

What happened next, reported in the journal Translational Neurodegeneration, is the real story. Female mice treated with the vesicles performed better on memory tests, showed sharply less amyloid buildup, and had immune cells that shifted from an aggressive, inflamed state to a calmer one. Researchers then tested the same vesicles on brain cells grown in a lab dish from the skin cells of actual Alzheimer’s patients. Those human cells were protected from the damage the disease usually causes.

How a Nasal Spray Delivers Alzheimer’s Treatment to the Brain

Before testing whether the treatment worked, scientists had to confirm it could even reach the right place. They isolated the packets from placenta stem cells, checked their size (mostly between 50 and 200 nanometers, far smaller than a single human cell), and confirmed they carried the right protein markers to count as genuine vesicles. Six separate batches came from six different placental donors, lowering the odds that results depended on one unusual sample.

After tagging the vesicles with a glowing dye and spraying them into mouse noses, researchers found evidence of them in every part of the hippocampus within hours. Neurons and microglia alike had absorbed the material, proof that a simple nasal spray could get therapeutic cargo past the barrier that normally keeps most substances out of the brain.

Female mice in the study carry genetic changes that cause Alzheimer’s-like brain damage as they age, and prior research shows these female mice tend to develop symptoms earlier and more severely than males, mirroring the pattern seen in human patients. Starting at three months old, before symptoms appeared, mice received either the vesicle treatment or a saltwater solution twice a week through the nose, continuing until they turned nine months old.

Along the way, mice took several classic memory tests: recognizing new objects, noticing when something in their environment moved, and navigating a maze that tests short-term memory. Treated mice outperformed untreated ones on the object-recognition and spatial-memory tests after both three and six months of treatment, and they also showed significantly better performance on the maze-navigation test after six months. Treatment even helped when started later, after disease-like changes had already set in, though the benefit showed up mainly in one test rather than all of them.

Alongside better memory, treated mice had far less of the sticky protein buildup called amyloid-beta in their hippocampus, with testing showing more than a 50 percent reduction. A separate hallmark of Alzheimer’s, the tangled protein called tau, showed no change, suggesting the vesicles target one piece of the disease rather than fixing everything at once.

Calming an Overactive Immune Response

Perhaps the most compelling part of the study involves what happened to the brain’s immune cells. Chronic activation of microglia and a related support cell called astrocytes is now considered a major driver of Alzheimer’s, not just a side effect of it. Treated mice had fewer of both cell types crowded into vulnerable brain regions, and the microglia that remained looked physically different, shifting away from the enlarged, hyper-branched shapes seen in the untreated Alzheimer’s mice toward simpler, less hypertrophic forms.

Markers that flag microglia as aggressively activated dropped after treatment, while markers tied to a calmer, repair-focused state rose sharply. Chemical signaling in the hippocampus shifted too, with several inflammation-promoting signals decreasing and protective ones increasing. Levels of proteins tied to healthy brain cell connections, including one called BDNF that helps neurons grow, also rose, hinting at a rebuilding process running alongside the calming effect.

To figure out what inside the vesicles actually caused this, researchers analyzed their cargo of microRNAs, tiny genetic snippets that act like dimmer switches for genes. The vesicles were packed with molecules already known to calm immune responses and support nerve health. When scientists stripped the vesicles of their RNA cargo and tested the emptied-out versions on inflamed microglia in a dish, the vesicles lost most of their calming power. That points to the RNA cargo, not just the vesicle’s outer shell, as the active ingredient.

From Mouse Brains to Human Alzheimer’s Neurons

A final piece of evidence came from human cells. Researchers took skin samples from people diagnosed with Alzheimer’s and from healthy volunteers of similar age, reprogrammed those cells into stem cells, and coaxed them into becoming brain cells. Neurons made from Alzheimer’s patients showed a well-documented problem: the branches that normally reach out to connect with other neurons started shrinking within about two weeks.

Adding the placenta-derived vesicles to these human cells during development largely prevented that shrinkage and restored levels of proteins needed for cell-to-cell communication, all without harming the cells. When researchers repeated the test with vesicles stripped of their RNA cargo, the protective effect weakened again, reinforcing that the genetic cargo drives the therapy’s power.

What This Could Mean for Future Alzheimer’s Treatment

Alzheimer’s has resisted decades of drug development, and much of that effort has centered on clearing amyloid rather than on the inflammation that keeps damaging the brain. This research adds to a growing case that the immune system inside the brain isn’t a bystander in this disease but an active participant that can potentially be coaxed back toward balance. A nasal spray built from placenta stem cell vesicles is still a long way from a pharmacy shelf, but the fact that it worked in both a mouse model and human brain cells taken from actual patients gives this approach two independent layers of evidence that are hard to dismiss.

Disclaimer: This article summarizes findings from a single peer-reviewed study conducted in mice and in lab-grown human cells. The nasal-spray treatment described has not been tested in people, and results in animal and cell models do not always translate to humans. Nothing here is medical advice. Anyone with questions about Alzheimer’s disease or treatment options should consult a qualified healthcare professional.