New Insights on Alzheimer’s Disease and Possible Treatment Source

Amyloid-beta and tau proteins are well-known signs of Alzheimer’s disease, yet they aren’t the sole factors contributing to the illness. Another element linked to cognitive decline comes from the ongoing activation of certain brain cells, particularly microglia and astrocytes, which can inflict damage on neurons due to neuroinflammation.

Recent research published in Translational Neurodegeneration has revealed a potential way to combat this inflammation, surprisingly sourced from the placenta. A team at the Catholic University of the Sacred Heart in Italy conducted experiments on mice where they administered a nasal formulation containing extracellular vesicles derived from placental cells.

“There is a promising direction in regenerative medicine focused on utilizing the therapeutic properties of extracellular vesicles, especially those from mesenchymal stromal cells (MSCs),” explained Andrea Papait, the lead author and a cell biologist of the study. These MSC-derived extracellular vesicles (MSC-EVs) are tiny particles that help cells communicate and may carry bioactive compounds that have anti-inflammatory and neuroprotective benefits.

For their study, the team used a specific type of MSC-derived EV, known as human amniotic mesenchymal stromal cell-derived vesicles (hAMSC-EVs), obtained from the amniotic membrane. The mice, genetically modified to show Alzheimer’s characteristics, received doses of this experimental nasal spray twice weekly for six months, starting at three months old, well before any Alzheimer’s-like symptoms appeared, and continuing until they were nine months old.

Through tests involving fluorescent dyes, researchers confirmed that the hAMSC-EVs successfully reached various parts of the hippocampus, linking with both neurons and microglia. Notably, behavior tests indicated that the treated mice showed better cognitive abilities than the control group in tasks related to object recognition and spatial memory.

The treatment led to a notable reduction in amyloid-beta build-up within the hippocampus, though it didn’t affect tau phosphorylation. Additionally, there was a significant decrease in neuroinflammation signs among the treated mice, evidenced by reduced activation of astrocytes and microglia. The treatment also seemed to enhance the levels of proteins related to neuroplasticity, such as ARC, GluA1, and BDNF.

In another lab experiment, skin cells from individuals with sporadic Alzheimer’s were converted into stem cells and then differentiated into neurons. The EV treatment effectively diminished neuronal deterioration and returned healthier levels of neuroplasticity-related protein expression.

These results build on earlier studies from the same team, suggesting that placenta-derived MSCs might have significant immune-modulating abilities, potentially setting the stage for innovative Alzheimer’s treatments down the line.

The researchers noted, “Our findings suggest that hAMSC-EVs can reduce neuroinflammation by changing the inflammatory microenvironment, rather than by direct immunosuppression.” The researchers also indicated that the modifications in microglial characteristics, cytokine profiles, and neuroplasticity-related factors hint at a supportive environment that bolsters neuronal health and synaptic functionality.

Nonetheless, while these results are promising, the researchers caution that it remains uncertain if similar positive outcomes would occur in humans experiencing cognitive decline. Future studies will likely explore these possibilities and delve deeper into the molecular mechanisms behind these neuroprotective effects.

“These are preliminary results that need further validation in humans and should not be considered an available therapy for Alzheimer’s at this stage, but they point to an encouraging path forward,” noted senior researcher and neuroscientist Claudio Grassi. He emphasized that understanding the placenta’s role in inflammation regulation might provide new avenues for treating neurodegenerative diseases and that the use of extracellular vesicles could represent an exciting new direction in neurological treatment.

The findings are presented in Translational Neurodegeneration.