A Specific Enzyme-Linked Immunosorbent Assay for Measuring β-Amyloid Protein Oligomers in Human Plasma and Brain Tissue of Patients With Alzheimer Disease

单体 阿尔茨海默病 脑组织 抗体 体内 化学 二聚体 β淀粉样蛋白 淀粉样蛋白(真菌学) 医学 病理 分子生物学 疾病 内科学 生物化学 免疫学 生物 遗传学 有机化学 聚合物
作者
Weiming Xia,Ting Yang,Ganesh M. Shankar,Imelda M. Smith,Yong Shen,Dominic M. Walsh,Dennis J. Selkoe
出处
期刊:Archives of neurology [American Medical Association]
卷期号:66 (2) 被引量:208
标识
DOI:10.1001/archneurol.2008.565
摘要

Objective: To examine in vivo levels of ␤-amyloid (A␤) oligomers (oA␤) vs monomeric A␤ in plasma and brain tissue of patients with sporadic and familial Alzheimer disease (AD) using a new enzyme-linked immunosorbent assay (ELISA) specific for oA␤.Design: To establish the oA␤ ELISA, the same Nterminal A␤ antibody was used for antigen capture and detection.Plasma and postmortem brain tissue from patients with AD and control subjects were systematically analyzed by conventional monomeric A␤ and new oA␤ ELISAs. Subjects:We measured oA␤ species in plasma samples from 36 patients with clinically well-characterized AD and 10 control subjects.In addition, postmortem samples were obtained from brain autopsies of 9 patients with verified AD and 7 control subjects.Main Outcome Measures: Oligomeric A␤ and 4 monomeric A␤ species in plasma samples from patients with AD and control subjects were measured by ELISA. Results:The specificity of the oA␤ ELISA was validated with a disulfide-crossed-linked, synthetic A␤ 1-40 Ser26Cys dimer that was specifically detected before but not after the dissociation of the dimers in ␤-mercaptoethanol.Plasma assays showed that relative oA␤ levels were closely associated with relative A␤ 42 monomer levels across all of the subjects.Analysis of sequential plasma samples from a subset of the patients with AD, including a patient with AD caused by a presenilin mutation, revealed decreases in both oA␤ and A␤ 42 monomer levels over a 1-to 2-year period.In brain tissue from 9 patients with AD and 7 control subjects, both oA␤ and monomeric A␤ 42 levels were consistently higher in the AD cases.Conclusions: An oA␤-specific ELISA reveals a tight link between oA␤ and A␤ 42 monomer levels in plasma and brain.Both forms can decline over time in plasma, presumably reflecting their increasing insolubility in the brain.
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