Recent research from the University of Virginia (UVA) School of Medicine has identified a potential target for preventing the loss of social memory in patients with Alzheimer’s disease (AD). This breakthrough revolves around specific brain cell structures called perineural nets, which play a crucial role in maintaining cognitive function. The study suggests that by focusing on these delicate structures, it may be possible to halt the progression of this devastating aspect of cognitive decline.
The team, led by Sontheimer, chair of UVA’s Department of Neuroscience, initially uncovered the significance of perineural nets in AD neurodegeneration in July 2024. They found that when these nets are compromised, the brain struggles to recall social connections, leading to the heart-wrenching experience of Alzheimer’s patients failing to recognize loved ones. “Finding a structural change that explains a specific memory loss in Alzheimer’s is very exciting,” Sontheimer stated.
Perineural nets, which were first discovered by Camillo Golgi in 1898, envelop inhibitory neurons that are essential for regulating brain activity. These structures slow down signals from excitatory nerve cells. Damage to the nets in Alzheimer’s can disrupt the ability of specialized support cells, known as astrocytes, to remove excess potassium and glutamate from the synapse connecting neurons. This malfunction can result in glutamate leaking into areas where it shouldn’t, potentially leading to the death of neighboring neurons.
In their experiments with a mouse model, researchers observed that damage to perineural nets resulted in a loss of social memory. Mice were unable to recognize familiar companions, despite retaining object recognition capabilities. This aligns with the experiences of Alzheimer’s patients, who often retain the ability to recognize objects even as they forget faces of family and friends. When the perineural nets remained intact, the mice demonstrated a marked ability to recognize familiar animals.
“Our research shows that when we preserve these brain structures early in life, mice suffering from this disease are better at remembering their social interactions,” said Lata Chaunsali, a graduate student involved in the study. This finding offers hope for a nontraditional approach to treating or even preventing Alzheimer’s disease, a pressing need in today’s society.
To explore this further, the team utilized matrix metalloproteinase (MMP) inhibitors—drugs primarily being studied in cancer research—to prevent AD-related damage to the perineural nets in mice. The treatment effectively halted the destruction of these structures, indicating a potential new avenue for therapeutic intervention.
While these findings are promising, Sontheimer cautioned that more research is necessary to determine the safety and effectiveness of this approach before it can be applied to human patients. “Although we have drugs that can delay the loss of perineuronal nets and consequently delay memory loss in the disease, further studies are needed,” he noted.
An intriguing aspect of this research is that the loss of perineuronal nets occurred independently of amyloid and plaque pathology, challenging the prevailing notion that these protein aggregates are the primary drivers of Alzheimer’s disease.
The findings from this pivotal study have been published in the journal Alzheimer’s & Dementia, marking a significant step forward in understanding and potentially mitigating the effects of Alzheimer’s on social memory. As research continues, the hope is that these insights will lead to effective strategies for preserving cognitive function in those affected by this challenging condition.
