唐氏综合征和阿尔茨海默病患者可溶性淀粉样β原纤维升高。

Elevated soluble amyloid beta protofibrils in Down syndrome and Alzheimer's disease.

机构信息

BioArctic AB, Warfvinges väg 35, SE-112 51 Stockholm, Sweden.

BioArctic AB, Warfvinges väg 35, SE-112 51 Stockholm, Sweden; Dept. of Public Health/Geriatrics, Uppsala University, SE-751 22 Uppsala, Sweden.

出版信息

Mol Cell Neurosci. 2021 Jul;114:103641. doi: 10.1016/j.mcn.2021.103641. Epub 2021 Jun 4.

DOI:10.1016/j.mcn.2021.103641

PMID:34091073

Abstract

Down syndrome (DS) is caused by trisomy of chromosome 21, which leads to a propensity to develop amyloid β (Aβ) brain pathology in early adulthood followed later by cognitive and behavioral deterioration. Characterization of the Aβ pathology is important to better understand the clinical deterioration of DS individuals and to identify interventive strategies. Brain samples from people with DS and Alzheimer's disease (AD), as well as non-demented controls (NDC), were analyzed with respect to different Aβ species. Immunohistochemical staining using antibodies towards Aβ was also performed. Elevated levels of soluble Aβ protofibrils and insoluble Aβx-40 and Aβx-42 in formic acid brain extracts, and elevated immunohistochemical staining of Aβ deposits were demonstrated with the antibody BAN2401 (lecanemab) in DS and AD compared with NDC. These data and the promising data in a large phase 2 CE clinical trial with lecanemab suggest that lecanemab may have the potential to preserve cognitive capacity in DS. Lecanemab is currently in a phase 3 CE clinical trial.

摘要

唐氏综合征（DS）是由 21 号染色体三体引起的，这导致患者在成年早期容易发展出淀粉样β（Aβ）脑病理学，随后出现认知和行为恶化。对 Aβ 病理学的特征进行分析对于更好地理解 DS 个体的临床恶化以及确定干预策略非常重要。对唐氏综合征和阿尔茨海默病（AD）患者以及非痴呆对照（NDC）的脑样本进行了分析，以研究不同的 Aβ 种类。还使用针对 Aβ 的抗体进行了免疫组织化学染色。与 NDC 相比，在甲酸脑提取物中可检测到可溶性 Aβ 原纤维和不溶性 Aβx-40 和 Aβx-42 的水平升高，并且用抗体 BAN2401（lecanemab）对 Aβ 沉积物的免疫组织化学染色也升高。这些数据以及 lecanemab 在一项大型 2 期 CE 临床试验中的有希望的数据表明，lecanemab 可能具有保护 DS 认知能力的潜力。lecanemab 目前正在进行 3 期 CE 临床试验。