As the most common form of dementia in the world, Alzheimer's disease (AD) is a progressive neurological disorder marked by cognitive and behavioral impairment. According to previous researches, abundant social connections shield against dementia. However, it is still unclear how exactly social interactions benefit cognitive abilities in people with AD and how this process is used to increase their general cognitive performance. In this study, we found that single novel social (SNS) stimulation promoted c-Fos expression and increased the protein levels of mature ADAM10/17 and sAPPα in the ventral hippocampus (vHPC) of wild-type (WT) mice, which are hippocampal dorsal CA2 (dCA2) neuron activity and vHPC NMDAR dependent. Additionally, we discovered that SNS caused similar changes in an AD model, FAD^4T mice, and these alterations could be reversed by α-secretase inhibitor. Furthermore, we also found that multiple novel social (MNS) stimulation improved synaptic plasticity and memory impairments in both male and female FAD^4T mice, accompanied by α-secretase activation and Aβ reduction. These findings provide insight into the process underpinning how social interaction helps AD patients who are experiencing cognitive decline, and we also imply that novel social interaction and activation of the α-secretase may be preventative and therapeutic in the early stages of AD.

作为世界上最常见的痴呆症，阿尔茨海默病（AD）是一种进行性神经系统疾病，以认知和行为障碍为特征。根据之前的研究，丰富的社会关系可以预防痴呆症。然而，目前尚不清楚社交互动究竟如何有益于 AD 患者的认知能力，以及如何利用这一过程来提高他们的总体认知表现。在这项研究中，我们发现单一新型社交（SNS）刺激促进了野生型（WT）小鼠腹侧海马（vHPC）中c-Fos的表达并增加了成熟ADAM10/17和sAPPα的蛋白质水平。背侧 CA2 (dCA2) 神经元活动和 vHPC NMDAR 依赖。此外，我们发现 SNS 在 AD 模型（FAD ^4T小鼠）中引起类似的变化，并且这些变化可以通过 α-分泌酶抑制剂逆转。此外，我们还发现，多种新型社交（MNS）刺激改善了雄性和雌性 FAD ^4T小鼠的突触可塑性和记忆障碍，并伴有 α-分泌酶激活和 Aβ 减少。这些发现提供了对社交互动如何帮助认知能力下降的 AD 患者的基础过程的深入了解，我们还暗示新的社交互动和 α-分泌酶的激活可能在 AD 的早期阶段具有预防和治疗作用。