Yang Johnson Chia-Shen, Kuo Pao-Jen, Chang Chad, Wang Yu-Ming, Ou Yu-Che, Cheng Yu-Chi, Wu Shao-Chun, Chien Peng-Chen, Hsieh Ching-Hua, Lin Wei-Che
From the Lymphedema Center, Division of Plastic and Reconstructive Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Plast Reconstr Surg Glob Open. 2025 Jul 29;13(7):e6955. doi: 10.1097/GOX.0000000000006955. eCollection 2025 Jul.
Lymphedema and Alzheimer disease (AD) share common mechanisms involving oxidative stress and chronic inflammation. However, the link between these 2 conditions and the impact of lymphaticovenous anastomosis (LVA) has not been fully explored. This study aimed to evaluate their association by examining changes in AD biomarkers, inflammatory cytokines, and oxidative stress markers before and after LVA.
Twenty-four patients with unilateral lower limb lymphedema who underwent LVA as primary treatment and 18 healthy controls were recruited. Exclusion criteria included previous LVA, liposuction, or excisional surgery. Venous blood samples were obtained before and 1 month after LVA.
After matching, 15 patients remained in each group. The lymphedema group had significantly elevated levels of t-tau (p < 0.001), amyloid beta (Aβ) ( = 0.033), Aβ ( = 0.033), Aβ × t-tau ( < 0.001), and Aβ/Aβ ratio ( = 0.021) compared with controls. One month post-LVA, there were significant reductions in t-tau ( = 0.007) and Aβ × t-tau ( = 0.002), and a notable increase in brain-derived neurotrophic factor ( = 0.006). Post-LVA samples also showed significant improvements in antioxidative enzymes, antioxidant capacity, and reductions in lipid peroxidation. Inflammatory cytokine levels were also significantly reduced, indicating decreased oxidative stress and inflammation. The median follow-up period was 6.3 months.
Findings suggest a possible association between lymphedema and increased AD risk possibly linked to elevated oxidative stress and inflammation. LVA may modulate this risk by reducing AD biomarkers and systemic inflammation/oxidative stress, supporting further investigation into its neuroprotective potential.
淋巴水肿与阿尔茨海默病（AD）具有涉及氧化应激和慢性炎症的共同机制。然而，这两种病症之间的联系以及淋巴静脉吻合术（LVA）的影响尚未得到充分探索。本研究旨在通过检查LVA前后AD生物标志物、炎性细胞因子和氧化应激标志物的变化来评估它们之间的关联。
招募了24例接受LVA作为主要治疗的单侧下肢淋巴水肿患者和18名健康对照。排除标准包括既往LVA、抽脂或切除手术。在LVA前和LVA后1个月采集静脉血样。
匹配后，每组各有15例患者。与对照组相比，淋巴水肿组的总tau蛋白（t-tau）（p < 0.001）、β-淀粉样蛋白（Aβ）（ = 0.033）、Aβ（ = 0.033）、Aβ×t-tau（ < 0.001）和Aβ/Aβ比值（ = 0.021）水平显著升高。LVA后1个月，t-tau（ = 0.007）和Aβ×t-tau（ = 0.002）显著降低，脑源性神经营养因子显著增加（ = 0.006）。LVA后的样本还显示抗氧化酶、抗氧化能力显著改善，脂质过氧化减少。炎性细胞因子水平也显著降低，表明氧化应激和炎症减轻。中位随访期为6.3个月。
研究结果表明淋巴水肿与AD风险增加之间可能存在关联，可能与氧化应激和炎症升高有关。LVA可能通过降低AD生物标志物和全身炎症/氧化应激来调节这种风险，支持对其神经保护潜力的进一步研究。
