Lecanemab and Vascular-Amyloid Deposition in Brains of People With Down Syndrome.

IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY
Lei Liu, Adriana Saba, Jesse R Pascual, Michael B Miller, Elizabeth L Hennessey, Ira T Lott, Adam M Brickman, Donna M Wilcock, Jordan P Harp, Frederick A Schmitt, Dennis J Selkoe, Jasmeer P Chhatwal, Elizabeth Head
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引用次数: 0

Abstract

Importance: 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.

Objective: 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.

Exposure: The binding properties of lecanemab were assessed in brain tissue.

Main outcome: The primary outcome was the extent of lecanemab binding to amyloid plaques and brain blood vessels.

Results: 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.

Conclusions and relevance: 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.

乐卡单抗与唐氏综合征患者大脑中的血管淀粉样蛋白沉积。
重要性:越来越多的阿尔茨海默病(AD)患者可以使用利卡尼单抗(lecanemab)进行抗β淀粉样蛋白免疫治疗。唐氏综合征(DS)患者在40岁之前就会出现阿尔茨海默病神经病理学症状,是由基因决定的阿尔茨海默病的重要群体:调查莱卡奈单抗在唐氏综合征患者大脑中的结合特性,以便将他们纳入临床试验或获得抗淀粉样蛋白免疫疗法:研究包括对15名年龄在43至68岁之间的DS患者的死后脑组织进行分析,这些病例于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。数据分析时间为2023年8月至2024年5月。暴露:评估利卡单抗在脑组织中的结合特性:主要结果:主要结果是lecanemab与淀粉样蛋白斑块和脑血管的结合程度:研究共纳入了 15 名年龄在 43 岁至 68 岁(平均 56.6 岁)的 DS 患者(8 名女性 [53%])的组织。在研究的所有 15 例 DS 患者中都出现了来卡尼单抗标记的淀粉样蛋白斑块,这表明可能存在靶点参与。然而,在 DS 中观察到莱卡尼单抗与脑血管广泛结合,这引起了人们对安全性的极大关注。这些发现强调了在DS患者中进行莱卡奈单抗临床试验以评估其安全性和有效性的必要性,尤其是在43岁以上的患者中:这些研究结果表明,来卡尼单抗与DS患者的脑淀粉样血管病有明显的结合。应在针对DS人群的AD临床试验中对莱卡尼单抗进行严格测试,以确定其安全性和有效性,尤其是在43岁以上的人群中。
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来源期刊
JAMA neurology
JAMA neurology CLINICAL NEUROLOGY-
CiteScore
41.90
自引率
1.70%
发文量
250
期刊介绍: JAMA Neurology is an international peer-reviewed journal for physicians caring for people with neurologic disorders and those interested in the structure and function of the normal and diseased nervous system. The Archives of Neurology & Psychiatry began publication in 1919 and, in 1959, became 2 separate journals: Archives of Neurology and Archives of General Psychiatry. In 2013, their names changed to JAMA Neurology and JAMA Psychiatry, respectively. JAMA Neurology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications.
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