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.
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.
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.
The specificity of the oAβ ELISA was validated with a disulfide–crossed-linked, synthetic Aβ1-40Ser26Cys 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.
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.