单体
阿尔茨海默病
脑组织
抗体
体内
化学
二聚体
酶
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
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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