Researchers have demonstrated that intranasally administered amniotic membrane-derived nanovesicles travel to the hippocampus, modulate neuroinflammation and synaptic integrity, and counteract cognitive decline in both animal models and human neurons.
A nasal spray containing extracellular vesicles naturally released by cells could help combat Alzheimer’s disease, according to research by scientists at Università Cattolica, Fondazione Policlinico Universitario A. Gemelli IRCCS and the E. Menni Research Center of Fondazione Poliambulanza.
The experimental treatment uses extracellular vesicles derived from the amniotic membrane, the tissue surrounding the developing baby during pregnancy. In the study published in Translational Neurodegeneration, the researchers found that the vesicles reached the brain in an experimental model of Alzheimer’s disease, reduced neuroinflammation, protected neuronal function and helped preserve memory.
The researchers also reported positive findings in experiments using human neurons grown in the laboratory.
Vesicles target the hippocampus
When administered through the nose to an animal model designed to mimic features of Alzheimer’s disease, the nanovesicles travelled to the hippocampus, a brain region central to memory and particularly vulnerable to Alzheimer’s-related damage.
Once there, the vesicles entered both neurons and microglia. These specialised cells are involved in monitoring and defending the brain.
The treatment appeared to influence several processes associated with Alzheimer’s disease. These included neuroinflammation and neuronal function, as well as the health of synapses, the connections through which information is transmitted between nerve cells.
According to the researchers, these effects were associated with significant improvements in cognitive abilities. The vesicles appeared to prevent memory deficits from developing while also counteracting cognitive decline after it had already emerged.
Testing the approach in human neurons
Fondazione Policlinico Universitario A. Gemelli IRCCS helped give the research a translational element. At its Memory Clinic, researchers collected skin biopsies from people with Alzheimer’s disease and healthy participants.
The cells were used to generate pluripotent stem cells and subsequently human neurons, allowing the researchers to investigate the effects of the extracellular vesicles in human experimental models.
The study was led by Dr Andrea Papait, a researcher in Cellular and Applied Biology, and Dr Francesca Natale, a researcher in Physiology. Their work brought together research into the biological and immunomodulatory properties of amniotic extracellular vesicles with their effects on neuroinflammation, neuronal function and memory.
Looking ahead
The researchers say the findings provide a basis for further investigation into extracellular vesicles as a potential treatment approach for Alzheimer’s disease. The ability to deliver the vesicles through the nose and reach the hippocampus could offer a non-invasive way of targeting processes involved in neuroinflammation and neuronal damage.
However, the positive findings in animal models and laboratory-grown human neurons will need to be followed by further studies to establish the treatment’s safety, effectiveness and appropriate dosage in people with Alzheimer’s disease.
If these results can be replicated in future research, amniotic extracellular vesicles could then become a new avenue for therapies aimed at protecting brain function and slowing or preventing cognitive decline.
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