A specific enzyme-linked immunosorbent assay for measuring β-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer Disease

Weiming Xia, Ting Yang, Ganesh Shankar, Imelda M. Smith, Yong Shen, Dominic M. Walsh, Dennis J. Selkoe

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

Abstract

Objective: To examine in vivo levels of β-amyloid (A(3) oligomers (oAβ) vs monomeric Aβ in plasma and brain tissue of patients with sporadic and familial Alzheimer disease (AD) using a new enzyme-linked immunosor-bent assay (ELISA) specific for oAβ. Design: To establish the oAβ ELISA, the same N-terminal Aβ 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 Aβand new oAβ ELISAs. Subjects: We measured oAβ 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 Aβ and 4 mo-nomeric Aβ species in plasma samples from patients with AD and control subjects were measured by ELISA. Results: The specificity of the oAβ ELISA was validated with a disulfide-crossed-linked, synthetic Aβ 1-40Ser26Cys dimer that was specifically detected before but not after the dissociation of the dimers in β-mercaptoethanol. Plasma assays showed that relative oAβ levels were closely associated with relative Aβ 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 oAβand Aβ 42 monomer levels over a 1-to 2-year period. In brain tissue from 9 patients with AD and 7 control subjects, both oAβand monomeric Aβ 42 levels were consistently higher in the AD cases. Conclusions: An oAβ-specific ELISA reveals a tight link between oAβ and Aβ 42 monomer levels in plasma and brain. Both forms can decline over time in plasma, presumably reflecting their increasing insolubility in the brain.

Original languageEnglish (US)
Pages (from-to)190-199
Number of pages10
JournalArchives of neurology
Volume66
Issue number2
DOIs
StatePublished - Feb 2009
Externally publishedYes

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

Fingerprint

Dive into the research topics of 'A specific enzyme-linked immunosorbent assay for measuring β-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer Disease'. Together they form a unique fingerprint.

Cite this