Scientists have tested an unusual experimental approach to Alzheimer’s disease: delivering tiny biological packages derived from human placental cells through the nose and into the brain.
In a new study published in Translational Neurodegeneration, researchers isolated microscopic particles called extracellular vesicles from mesenchymal stromal cells found in the amniotic membrane of donated human placentas.
They then administered those vesicles into the noses of female mice genetically engineered to develop features of Alzheimer’s disease.
The results were striking.
Mice that received the treatment performed better on several memory tests, showed less amyloid-beta accumulation in the hippocampus, and had signs of reduced inflammation in the brain. The researchers also found evidence that the treatment affected microglia and astrocytes, cells increasingly implicated in the progression of Alzheimer’s disease.
The vesicles even reached the hippocampus after being administered through the nose, where researchers detected them inside neurons and microglia.
But there’s an enormous caveat.
This isn’t an Alzheimer’s nasal spray that’s available to patients, and it hasn’t yet been tested as a treatment in humans.
The findings come primarily from mice, along with laboratory experiments using neurons derived from a small number of people with sporadic Alzheimer’s disease. The researchers themselves describe the results as preclinical and say they require validation in humans.
What Exactly Came From the Placenta?
Despite how strange “placenta-derived nasal treatment” might sound, the researchers weren’t administering placental tissue.
They obtained human amniotic mesenchymal stromal cells, or hAMSCs, from the amniotic membrane of donated full-term placentas. According to the published study, the placentas came from healthy donors following vaginal delivery or cesarean section with informed consent.
Cells naturally release tiny membrane-bound packages called extracellular vesicles, or EVs. These particles can carry molecular cargo between cells, including proteins, lipids, and genetic material such as microRNAs.
Researchers isolated these vesicles from the placental cells and used them as the experimental treatment.
That difference matters. The scientists are essentially investigating whether some of the biological signals packaged by these cells can be harnessed therapeutically without transplanting the cells themselves.
What Happened When Researchers Gave Them to Mice?
The main experiment used female 3×Tg-AD mice, a genetically engineered model that develops several features associated with Alzheimer’s disease.
Beginning at three months of age, before cognitive impairment had appeared, the mice received either the extracellular vesicles or saline twice a week through the nose until nine months of age.
Researchers then put them through several tests designed to assess recognition and spatial memory.
The treated mice performed better.
Their brains also showed biological differences. Hippocampal amyloid-beta levels were lower, including an approximately 53% reduction in one measure of Aβ. Researchers observed reduced activation of microglia and astrocytes and changes in inflammatory signaling. Proteins involved in neuroplasticity, including BDNF, GluA1, and ARC, were also increased.
One thing the treatment did not appear to change was tau phosphorylation. That’s important because it shows the treatment wasn’t simply reversing every feature of Alzheimer’s-like pathology in the mice.
The researchers also conducted a smaller experiment beginning when the mice were nine months old and already showing Alzheimer’s-like changes. After one month of treatment, the mice improved on one recognition-memory test but not another.
That makes the findings more complicated than simply saying the treatment “reversed Alzheimer’s.” The strongest results came when treatment began before cognitive impairment developed.
How Could Something Put in the Nose Reach the Brain?
Getting experimental treatments into the brain presents a major challenge because of the blood-brain barrier, which restricts many substances circulating in the bloodstream from entering brain tissue.
Intranasal delivery is therefore being investigated as one possible route for delivering certain therapeutics to the central nervous system.
In this experiment, the researchers actually checked where the extracellular vesicles went.
After fluorescently labeling them, they detected the vesicles in the hippocampus following intranasal administration. Some were found inside neurons and microglia.
That finding is particularly important to the proof of concept. It suggests that at least some of the vesicles administered through the nose were able to reach the brain region the researchers were attempting to influence.
Whether the same delivery method would work as effectively in humans is another question.
The Treatment Appeared to Change the Brain’s Inflammatory Environment
Alzheimer’s research has traditionally focused heavily on amyloid-beta plaques and tau tangles. But researchers are also investigating the role of neuroinflammation and cells such as microglia and astrocytes in how the disease develops and progresses.
The new study suggests the extracellular vesicles may influence this environment.
Treated mice showed changes involving microglia and astrocytes in vulnerable brain regions, along with alterations in inflammatory signaling.
When researchers analyzed the microRNAs carried inside the vesicles, they also identified numerous molecules associated with pathways involved in immune regulation and neuroprotection.
Professor Salvatore Fusco, one of the researchers involved in the study, said the findings support looking beyond amyloid and tau and considering the cellular environment surrounding neurons and the signals exchanged between cells.
The researchers’ broader interpretation of the findings was described in a release accompanying the study.
That doesn’t mean inflammation has replaced amyloid or tau as “the cause” of Alzheimer’s. Rather, the study adds to research examining how several biological processes may interact as the disease progresses.
Researchers Also Tested Human Alzheimer’s Neurons
The researchers didn’t stop with mice.
They also generated neurons from induced pluripotent stem cells obtained from three people with sporadic Alzheimer’s disease and three healthy individuals.
The Alzheimer’s-derived neurons showed reduced neurite growth and lower levels of certain proteins involved in synaptic function.
When researchers exposed these cells to the placenta-derived extracellular vesicles, the treatment helped prevent neurite atrophy and restored some synaptic protein expression.
It’s an intriguing result because it shows that some of the biological effects weren’t confined entirely to the mouse model.
But these were human cells growing in a laboratory, not people receiving the treatment. With only three Alzheimer’s donors and three healthy controls, this part of the experiment was also extremely small.
Could This Become an Alzheimer’s Treatment?
The study provides evidence that extracellular vesicles derived from human amniotic stromal cells can reach the brains of mice following intranasal administration and influence several processes associated with Alzheimer’s-like disease.
That’s a promising proof of concept.
It is not evidence that a placenta-derived nasal treatment prevents or treats Alzheimer’s disease in people.
Mouse models reproduce selected features of Alzheimer’s disease but cannot capture the full complexity of the human condition. The main long-term experiment also involved female mice, while the human component consisted of laboratory-grown neurons from only a handful of donors.
The researchers acknowledge those limitations themselves.
Professor Claudio Grassi described the findings as preclinical and emphasized that they still require validation in humans, according to the research team’s announcement.
The next questions are substantial. Can these vesicles be produced consistently? What dose would be appropriate for humans? Can enough of them reach the human brain through the nose? Are repeated doses safe? And, most importantly, could they actually slow cognitive decline in people with Alzheimer’s disease?
Those answers will require human clinical trials.
For now, the study offers an intriguing idea: some of the biological signals produced by cells associated with the placenta may eventually help researchers find new ways to protect the aging brain.
Disclaimer: This information is not intended to be a substitute for professional medical advice, diagnosis or treatment and is for information only. Always seek the advice of your physician or another qualified health provider with any questions about your medical condition and/or current medication. Do not disregard professional medical advice or delay seeking advice or treatment because of something you have read here.
A.I. Disclaimer: This article was created with AI assistance and edited by a human for accuracy and clarity.
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