A team of Italian researchers has demonstrated that an experimental nasal spray containing tiny vesicles derived from the human placenta can reach the brain, reduce neuroinflammation, and protect memory in animal models of Alzheimer’s disease, according to a study published in Translational Neurodegeneration.
Placental Nasal Spray Shows Memory-Protecting Potential in Alzheimer’s Models
Alzheimer’s disease is the most common cause of dementia, progressively impairing memory, thinking, communication, and everyday functioning. While scientific research has traditionally concentrated on the accumulation of abnormal proteins such as beta-amyloid and tau, investigators increasingly recognize that chronic neuroinflammation and changes in the environment surrounding brain cells also contribute significantly to cognitive decline.
The collaborative research was conducted by teams from the Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, and the E. Menni Research Center of Fondazione Poliambulanza. The work combines the fields of cell biology, neuroscience, and regenerative medicine by investigating how natural anti-inflammatory signals from the placenta might be harnessed to combat neurodegenerative disease.
How the Placental Vesicles Target the Brain
The experimental treatment utilizes human amniotic mesenchymal stromal cell-derived vesicles, known as hAMSC-EVs, which are sourced from the amniotic membrane of the placenta. These nanoparticles act as mediators of intercellular communication, carrying bioactive molecules that possess anti-inflammatory and neuroprotective properties.
In the study, researchers administered the nasal spray formulation to transgenic mice genetically engineered to exhibit features of Alzheimer’s disease. Using fluorescent dyes, the scientists confirmed that the vesicles successfully traveled from the nasal passages into the brain, reaching all regions of the hippocampus—a structure crucial for learning and memory that is affected early in the course of Alzheimer’s disease.
Once inside the hippocampus, the vesicles entered both neurons and microglia, which are cells responsible for immune surveillance and defense within the central nervous system. Rather than simply suppressing the immune system, the treatment reshaped the inflammatory microenvironment by modifying the functional state and morphology of microglia, creating favorable conditions for neuronal integrity.
Cognitive Benefits and Human Cell Verification
The treatment yielded positive results across different stages of the experimental disease. When administered earlier, the vesicles prevented the onset of memory deficits; when given later, they counteracted cognitive decline that had already developed.
Behavioral evaluations demonstrated that treated animals performed better on cognitive tasks measuring recognition memory, spatial memory, and short-term working memory compared to control animals. Molecular analyses revealed that the therapy reduced neuronal deterioration, significantly decreased amyloid-beta deposits in the hippocampus, and increased the expression of proteins linked to neuroplasticity and synaptic transmission.
To evaluate whether these findings might translate to humans, researchers at the Gemelli Memory Clinic collected skin biopsies from Alzheimer’s patients and healthy volunteers. These samples were reprogrammed into pluripotent stem cells and developed into human neurons in the laboratory. The hAMSC-EV vesicles produced protective changes in these human neurons in vitro, supporting further investigation into the approach.
Lead Researchers and Future Directions
The study was led by cell biologist Andrea Papait and physiology researcher Francesca Natale, with senior contributions from Ornella Parolini, Claudio Grassi, and Salvatore Fusco. The findings suggest that a nasal formulation could offer a less invasive method for delivering biological materials toward the brain, pointing to a potential new frontier in the treatment of neurological conditions.
