New research from the University of Virginia (UVA) indicates that targeting specific brain structures could help prevent Alzheimer’s disease (AD) patients from losing their ability to recognize loved ones. The study reveals that disruptions in perineural nets—delicate structures surrounding brain cells—may play a critical role in the decline of social memory, a key aspect of cognitive function in Alzheimer’s.
In findings published in the journal Alzheimer’s & Dementia, scientists first identified the role of perineural nets in AD neurodegeneration in July 2024. The research suggests that as these structures degrade, the brain’s ability to recall social connections deteriorates. “Finding a structural change that explains a specific memory loss in Alzheimer’s is very exciting,” stated Sontheimer, Chair of UVA’s Department of Neuroscience and member of the UVA Brain Institute. “It is a completely new target, and we already have suitable drug candidates in hand.”
Researchers believe that when the perineural nets, which protect communicating nerve cells, are damaged, neurons struggle to form and store memories. Originally discovered by Camillo Golgi in 1898, these nets are now recognized as essential for brain health, more than previously understood. They surround inhibitory neurons, which regulate brain activity by slowing down signals from excitatory nerve cells. Damage to these nets in AD prevents support cells, known as astrocytes, from effectively clearing potassium and glutamate from synapses. This results in an overabundance of glutamate, which can be toxic to neighboring neurons.
In a controlled mouse model, researchers observed that when perineural nets were damaged, the mice lost their ability to recognize familiar peers, despite retaining other memory functions. This mirrors a common progression in Alzheimer’s patients, who may forget loved ones while still remembering objects or places. “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,” explained Lata Chaunsali, a graduate student involved in the study.
The team employed matrix metalloproteinase (MMP) inhibitors, which are primarily researched in cancer treatment, to block the damage to perineural nets in the mice. This intervention successfully halted the degradation of these structures. While the research is still in the preliminary stages, existing drugs may present an innovative approach to protect brain function as Alzheimer’s progresses.
“Although we have drugs that can delay the loss of perineuronal nets, and thereby delay memory loss in disease, more research needs to be done regarding the safety and effectiveness of our approach before this can be considered in humans,” Sontheimer remarked. Notably, the study found that the loss of perineuronal nets happens independently of amyloid and plaque pathology. This raises questions about the traditional understanding of these protein aggregates’ role in Alzheimer’s disease.
As the research continues, it has the potential to lead to new treatment options that could significantly improve the quality of life for those affected by Alzheimer’s, a condition that currently impacts millions of families worldwide.
