A Reproducible Supermicrosurgical Model of Cervical Lymphatic-Venous Anastomosis in Transgenic Alzheimer

Background: While cervical lymphatic-venous anastomosis (LVA) shows clinical promise for Alzheimer disease (AD), a validated, accessible preclinical model for mechanistic study is critically lacking. Building on our prior rat model, this study aimed to overcome the supermicrosurgical barrier of translating this technique to the mechanistically essential transgenic mouse and to establish a reproducible training paradigm. Methods: The junior surgeon underwent a 2-stage training program. An initial phase on 30 small, cost-effective Sprague-Dawley rats (60 anastomoses) was performed to master the technique before translation to 10 male 5×FAD mice (20 anastomoses). Surgical proficiency was quantitatively assessed using procedural time, UWOMSA scores, and CUSUM analysis. Patency was confirmed via ICG lymphangiography. Results: Anatomic measurements confirmed the supermicrosurgical challenge ( P <0.0001). The training was effective: proficiency was achieved after 27 anastomoses in rats and subsequently just 10 in mice. This mastery resulted in a 100% anastomotic patency rate in the 9 surviving 5×FAD mice. Conclusion: We successfully established a reproducible supermicrosurgical LVA model in a transgenic AD mouse. Crucially, we demonstrated that a staged training protocol makes this highly challenging technique accessible, providing a validated learning curve and a critical platform to advance the investigation of lymphatic-based therapies for AD.