Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Pathology and Laboratory Medicine, Department of Neurology, University of California, Irvine.
JAMA Neurol. 2024 Oct 1;81(10):1066-1072. doi: 10.1001/jamaneurol.2024.2579.
Anti-β-amyloid immunotherapy using lecanemab is becoming increasingly available to patients with Alzheimer disease (AD). Individuals with Down syndrome (DS) develop AD neuropathology by age 40 years, representing a significant cohort of genetically determined AD.
To investigate the binding properties of lecanemab in the brains of people with DS, in anticipation of their inclusion in clinical trials or access to antiamyloid immunotherapies.
DESIGN, SETTING, PARTICIPANTS: The study included cases of postmortem brain tissue analysis from 15 individuals with DS aged 43 to 68 years that were acquired from Alzheimer Disease research centers at the University of California, Irvine and the University of Kentucky from 2008 to 2021. Data were analyzed from August 2023 through May 2024.
The binding properties of lecanemab were assessed in brain tissue.
The primary outcome was the extent of lecanemab binding to amyloid plaques and brain blood vessels.
Tissue from 15 people (8 were female [53%]) with DS ranging in age from 43 to 68 (mean, 56.6) years were included in the study. Lecanemab-labeled amyloid plaques appeared in all 15 DS cases studied, indicating potential target engagement. However, extensive binding of lecanemab to brain blood vessels in DS was observed, raising significant safety concerns. These findings underscore the necessity for clinical trials of lecanemab in people with DS to evaluate both safety and efficacy, particularly in individuals older than 43 years.
These findings suggest significant binding of lecanemab to cerebral amyloid angiopathy in DS. Lecanemab should be rigorously tested in clinical trials for AD in the DS population to determine its safety and efficacy, especially in those older than 43 years.
抗β-淀粉样蛋白免疫疗法使用 lecanemab 正越来越多地应用于阿尔茨海默病（AD）患者。唐氏综合征（DS）患者在 40 岁时就会出现 AD 神经病理学表现，这是一个具有重大意义的遗传性 AD 群体。
研究 lecanemab 在 DS 患者大脑中的结合特性，以便在他们被纳入临床试验或获得抗淀粉样蛋白免疫疗法时做好准备。
设计、地点、参与者：本研究纳入了 2008 年至 2021 年期间，从加利福尼亚大学欧文分校和肯塔基大学的阿尔茨海默病研究中心获得的 15 名年龄在 43 至 68 岁的 DS 个体死后脑组织分析病例。数据于 2023 年 8 月至 2024 年 5 月进行分析。
评估了 lecanemab 在脑组织中的结合特性。
主要结果是 lecanemab 与淀粉样斑块和脑血管的结合程度。
研究纳入了 15 名 DS 患者（8 名女性[53%]）的组织，年龄从 43 岁至 68 岁（平均 56.6 岁）。在所有 15 例 DS 病例中均观察到 lecanemab 标记的淀粉样斑块，表明潜在的靶点结合。然而，在 DS 中观察到 lecanemab 对脑血管的广泛结合，引起了重大的安全性担忧。这些发现强调了在 DS 人群中进行 lecanemab 的临床试验评估安全性和疗效的必要性，特别是在年龄大于 43 岁的个体中。
这些发现表明 lecanemab 与 DS 中的脑动脉淀粉样变性有显著结合。在 DS 人群中进行 AD 的 lecanemab 临床试验应严格测试其安全性和疗效，尤其是在年龄大于 43 岁的人群中。
