New research from the University of Virginia (UVA) School of Medicine reveals that the deterioration of social memory in Alzheimer’s disease (AD) may be linked to specific structures surrounding brain cells. This discovery opens the door to potential interventions that could prevent patients from forgetting their loved ones.
The study, published in the journal Alzheimer’s & Dementia, builds on findings from July 2024, where scientists first identified the critical role of perineural nets in the neurodegeneration associated with AD. These structures are essential for maintaining the functions of neurons, which are vital for memory formation and retrieval. Dr. Sontheimer, chair of UVA’s Department of Neuroscience and a member of the UVA Brain Institute, emphasized the significance of this discovery. “Finding a structural change that explains a specific memory loss in Alzheimer’s is very exciting,” he stated. “It is a completely new target, and we already have suitable drug candidates in hand.”
The research suggests that disruptions to perineural nets contribute to the inability of neurons to form and store memories. Historically recognized as early as 1898 by Camillo Golgi, these nets surround inhibitory neurons that regulate brain activity. When damaged due to Alzheimer’s, the ability of specialized support cells, known as astrocytes, is compromised. This leads to an accumulation of glutamate in synapses, which can be toxic to neighboring neurons.
In experiments with a mouse model, researchers found that damage to perineural nets resulted in a loss of social memory. Mice could not recognize familiar companions, despite retaining other memory functions such as object recognition. This mirrors a common progression in Alzheimer’s patients, who often forget loved ones while still recalling other types of memories. “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 graduate student Lata Chaunsali.
The team utilized matrix metalloproteinase (MMP) inhibitors, primarily studied in cancer research, to protect perineural nets from AD-related damage in mice. Their findings indicate that these existing drugs could offer a novel approach to mitigate cognitive decline. “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 safety and effectiveness of our approach before this can be considered in humans,” Dr. Sontheimer noted.
Another intriguing aspect of the study is the independence of perineuronal net loss from amyloid and plaque pathology, which may challenge current understandings of Alzheimer’s disease. This suggests that the mechanisms behind memory loss may be more complex than previously thought.
As the research progresses, scientists are hopeful that these insights will lead to new strategies for preventing Alzheimer’s disease, addressing a significant healthcare challenge faced by millions worldwide.
