New findings from researchers at the University of Virginia (UVA) suggest that targeting specific brain structures could help prevent Alzheimer’s disease (AD) patients from losing their ability to recognize loved ones. The research focuses on perineural nets, delicate structures surrounding brain cells, which play a crucial role in maintaining social memory.
The UVA team originally identified the significance of these perineural nets in July 2024. They discovered that the degradation of these nets disrupts the brain’s capacity to recall social connections. According to Dr. Sontheimer, chair of UVA’s Department of Neuroscience, “Finding a structural change that explains a specific memory loss in Alzheimer’s is very exciting. It is a completely new target, and we already have suitable drug candidates in hand.”
Perineural nets serve as protective barriers for inhibitory neurons, which regulate brain activity by moderating signals from excitatory nerve cells. When Alzheimer’s damages these nets, specialized support cells, known as astrocytes, struggle to remove potassium and glutamate from synapses. This failure can cause glutamate to spill into unintended areas, potentially harming neighboring neurons.
In experiments with a mouse model, the researchers observed that damage to perineural nets led to a loss of social memory, as the mice could not recognize familiar companions. Notably, their ability to recognize objects remained unaffected, mirroring a common symptom in Alzheimer’s patients who may forget loved ones while retaining other memories.
The research demonstrated that when perineural nets were preserved, mice maintained their ability to recognize other animals. Lata Chaunsali, a graduate student involved in the study, stated, “In our research with mice, when we kept these brain structures safe early in life, the mice suffering from this disease were better at remembering their social interactions.” This finding highlights the potential for a new approach to treating or even preventing Alzheimer’s disease, an area urgently in need of innovative solutions.
To explore therapeutic options, the team utilized matrix metalloproteinase (MMP) inhibitors, which are primarily under investigation for cancer treatment, to protect perineural nets from Alzheimer’s-related damage in mice. This treatment effectively halted the deterioration of these structures. While the research is still in its early stages, these existing drugs could represent a groundbreaking method for safeguarding brain function as Alzheimer’s progresses.
Dr. Sontheimer cautioned that although the team has drugs that can delay the loss of perineuronal nets and, consequently, memory loss, further research is necessary to evaluate the safety and effectiveness of this approach for human patients. “One of the most interesting aspects of our research is the fact that the loss of perineuronal nets observed in our studies occurred completely independent of amyloid and plaque pathology, adding to the suspicion that those protein aggregates may not be causal of disease,” he explained.
The findings were published in the journal Alzheimer’s & Dementia, contributing valuable insights into the underlying mechanisms of memory loss associated with Alzheimer’s disease. As the search for effective treatments continues, this research offers hope for preserving social connections in individuals affected by cognitive decline.
