title: A Luminex assay detects amyloid β oligomers in Alzheimer's disease cerebrospinal fluid.
abstract: Amyloid beta (aβ) protein assembles into larger protein aggregates during the pathogenesis of Alzheimer's disease (AD) and there is increasing evidence that soluble aβ oligomers are a critical pathologic species. Diagnostic evaluations rely on the measurement of increased tau and decreased aβ42 in the cerebrospinal fluid (CSF) from AD patients and evidence for oligomeric aβ in patient CSF is conflicting. In this study, we have adapted a monoclonal single antibody sandwich ELISA assay to a Luminex platform and found that this assay can detect oligomerized aβ42 and sAPPα fragments. We evaluated oligomeric aβ reactivity in 20 patients with AD relative to 19 age matched controls and compared these values with a commercially available Alzbio3 kit that detects tau, phosphorylated tau and aβ42 on the same diagnostic platform. We found that CSF samples of patients with AD had elevated aβ oligomers compared to control subjects (p < 0.05) and the ratio of aβ oligomers to aβ42 was also significantly elevated (p < 0.0001). Further research to develop high sensitivity analytical platforms and rigorous methods of developing stable assay standards will be needed before the analysis of oligomeric aβ becomes a routine diagnostic assay for the evaluation of late onset AD patients.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America. azherskovits@partners.org
authors.forename: Adrianna Z
authors.initials: AZ
authors.lastname: Herskovits
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Locascio
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000737:chemistry; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000737:chemistry; D010766:Phosphorylation; D055503:Protein Multimerization; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins