This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on Web of Science (2)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Alzheimer Disease  • Cognitive Disorders  • Neurology, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

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

Arch Neurol. 2009;66(2):190-199.

Objective  To examine in vivo levels of β-amyloid (Aβ) oligomers (oAβ) vs monomeric Aβ in plasma and brain tissue of patients with sporadic and familial Alzheimer disease (AD) using a new enzyme-linked immunosorbent 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 Aβ and 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 monomeric 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 Aβ₄₂ 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 oAβ and Aβ₄₂ monomer levels over a 1- to 2-year period. In brain tissue from 9 patients with AD and 7 control subjects, both oAβ and monomeric Aβ₄₂ levels were consistently higher in the AD cases.

Conclusions  An oAβ-specific ELISA reveals a tight link between oAβ and Aβ₄₂ monomer levels in plasma and brain. Both forms can decline over time in plasma, presumably reflecting their increasing insolubility in the brain.

Author Affiliations: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (Drs Xia, Yang, Shankar, and Selkoe); UCD School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland (Ms Smith and Dr Walsh); and Haldeman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute, Sun City, Arizona (Dr Shen).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?