Social memory can fade earlier than other abilities in Alzheimer’s disease, yet the biological reason behind this painful loss has remained unclear. A new study from the University of Virginia uncovers a structural breakdown deep in the hippocampus that may explain why familiar faces suddenly become unrecognizable. The findings point to a specific vulnerability in the brain’s social memory system, and a potential path for future research.Scientists investigate why Alzheimer’s patients stop recognizing loved ones. Image by FreepikNote: This article is intended for general information and educational purposes. It summarizes scientific research in accessible language for a broad audience and is not an official scientific press release.The loss of the ability to recognize familiar people is often described as one of the most painful features of Alzheimer’s disease. Scientists have long known that different forms of memory decline at different rates, but the mechanisms behind this selective vulnerability have remained unclear. A new peer-reviewed study titled “Degradation of perineuronal nets in hippocampal CA2 explains the loss of social cognition memory in Alzheimer’s disease” offers an explanation grounded in the biology of a specific hippocampal region. The authors propose that structural degradation surrounding certain neurons may disrupt the brain’s ability to store and retrieve social memory, while other forms of memory – such as object recognition – were largely preserved in this model.The study was conducted by Lata Chaunsali, Jiangtao Li, Erik Fleischel, Courtney E. Prim, Izabela Kasprzak, Shan Jiang, Silky Hou, Miguel Escalante, Elise C. Cope, Michelle L. Olsen, Bhanu P. Tewari and Harald Sontheimer. The authors are affiliated with the Department of Neuroscience at the University of Virginia School of Medicine in Charlottesville, Virginia, USA, and the School of Neuroscience at Virginia Tech in Blacksburg, Virginia, USA. Their work appears in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.Alzheimer’s research has traditionally focused on amyloid plaques, tau pathology and the progressive loss of episodic memory. However, social memory – the ability to recognize familiar individuals – often deteriorates early in the disease. This selective decline raised questions about whether it follows the same trajectory as other cognitive impairments or whether it reflects changes in specific neural circuits.The new study focuses on the hippocampal CA2 region (a distinct subfield of the hippocampus known for its role in social memory and social-recognition processing), and on perineuronal nets (PNNs), which are extracellular structures that help stabilize neuronal activity. The authors sought to determine whether degradation of these structures might explain the loss of social recognition in Alzheimer’s disease models.How the study was conductedThe researchers used mice engineered to exhibit Alzheimer-like pathology. They examined the CA2 region for changes in PNN expression and organization. Using established staining techniques, they quantified the density and integrity of the nets and compared these measurements across Alzheimer-model mice and controls.To determine how structural changes translated into functional impairments, the authors performed behavioral tests assessing two forms of memory:Social recognition memory – the ability to distinguish a familiar mouse from a novel one.Object recognition memory – the ability to identify a familiar object versus a new one.This parallel approach allowed the researchers to determine whether the observed deficits were selective.The team also administered matrix metalloproteinase (MMP) inhibitors – compounds known to prevent extracellular matrix breakdown – to a subset of mice. The goal was to see whether preserving the integrity of PNNs would also preserve social recognition ability. Finally, they evaluated amyloid-related markers to clarify whether PNN degradation aligned with the established amyloid pathology or occurred independently.What makes this study newThis study stands out because it focuses on a structural change in the brain – not the usual amyloid buildup – to explain why social memory is lost in Alzheimer’s disease. The authors report that the CA2 region of the hippocampus, which is known to support social recognition, appears especially sensitive to damage when its perineuronal nets (PNNs) begin to break down. Their results suggest that this loss of PNN stability, rather than classical protein aggregates, may underlie the specific difficulty Alzheimer’s patients have in recognizing familiar people.According to the authors, previous research had already shown that CA2 is important for social memory, but its connection to Alzheimer-related changes had not been clearly defined. Their work identifies a direct link between PNN degradation in CA2 and the selective loss of social memory, providing a new structural explanation for a symptom commonly seen in the disease.Key findings from the studyAccording to the authors, the experiments led to several clear observations:In the Alzheimer’s-model mice, the perineuronal nets in the CA2 region of the hippocampus were noticeably weakened and showed significant breakdown.When these nets were degraded, the mice struggled to recognize familiar individuals, but their ability to recognize objects stayed mostly normal. This points to a very specific type of memory loss.When the researchers gave the mice MMP inhibitors, the protective nets stayed intact, and the mice continued to recognize other mice they had met before.The analyses showed that this breakdown of perineuronal nets occurred in a CA2 region that was largely devoid of amyloid-beta plaques, indicating that in this model the structural change did not spatially coincide with plaque deposition and may follow a pathway separate from classic amyloid pathology.The authors conclude that the CA2 region – and the extracellular structures that support it – may be especially vulnerable in this model, which helps explain why social recognition is affected before other forms of memory.Authors’ conclusionsThe authors explain that their results point toward a possible reason for the specific loss of social recognition in Alzheimer’s disease models: when the perineuronal nets in the CA2 region begin to break down, the circuits that support social memory become less stable. They describe CA2 as an important center for processing social information and suggest that its vulnerability may help explain why recognizing familiar people is affected so early.At the same time, the authors emphasize that their conclusions come from animal studies. They acknowledge that more research is needed to determine whether the same type of perineuronal-net changes occur consistently in humans with Alzheimer’s disease. They highlight the preservation of these nets as a promising scientific direction but do not make any claims about clinical use, treatment, or prevention.Understanding the broader contextThis research contributes to broader scientific efforts to understand how Alzheimer’s disease affects different forms of memory. It underscores that social recognition relies on specific neural circuits and structural supports in the CA2 region. By demonstrating that these structures are compromised independently of amyloid pathology, the study adds complexity to existing models of Alzheimer’s mechanisms. It also provides a new lens for interpreting why social cognition declines early in the disease.ConclusionThe study by Chaunsali and colleagues identifies a mechanism that specifically disrupts social recognition memory in Alzheimer’s disease models, while object-recognition abilities in the same models remained largely preserved. The work highlights the role of perineuronal nets in supporting CA2 function and shows that their degradation is closely associated with selective social-memory impairments in the mouse model used. While it is still uncertain how directly these findings apply to humans, the results broaden the scientific understanding of Alzheimer’s-related cognitive decline and point to structural features of the hippocampus as important targets for future research.The information in this article is provided for informational purposes only and is not medical advice. For medical advice, please consult your doctor.ReferencesChaunsali L., Li J., Fleischel E., Prim C. E., Kasprzak I., Jiang S., Hou S., Escalante M., Cope E. C., Olsen M. L., Tewari B. P., Sontheimer H. Degradation of perineuronal nets in hippocampal CA2 explains the loss of social cognition memory in Alzheimer’s disease. Alzheimer’s & Dementia (2025). DOI: https://doi.org/10.1002/alz.70813The post Scientists investigate why Alzheimer’s patients stop recognizing loved ones appeared first on CogniFit Blog: Brain Health News.