Abstract Details

Title Analytical and Clinical Validation of ß-Amyloid 1-40, 1-42, and the 1-42/1-40 Ratio Using a Clinical Autoanalyzer

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-014

Background PET imaging and measurements in CSF have been traditionally used to investigate the presence of β-amyloid plaques for diagnosis of Alzheimer’s disease (AD), but these approaches are costly and invasive¹. As an alternative, plasma-based measurements are currently being investigated to broaden testing accessibility.

Objective Validation of a high-throughput Aβ42/40 plasma assay.

Design/Methods The Sysmex HISCL^®-5000 Immunoassay System was used to validate immunoassays for the measurement of Aβ40 and Aβ42 in plasma samples to determine the Aβ42/40 ratio. Validation of these measurements included investigation of assay imprecision, analytical measurement range (AMR), common interferences as well as measurements of sample stability. In addition, clinically defined specimens² were measured to determine an appropriate cutoff with respect to β-amyloid PET results. The Aβ42/40 ratio of clinically defined samples was also measured using assays from two predicate assays.

Results Imprecision results produced within-laboratory CVs ≤ 6.5% for both Aβ40, Aβ42, as well as the Aβ42/40 ratio. The AMR of each assay was found to be suitable for measurements of anticipated plasma concentrations and acceptable levels of common assay interferents were identified. Sample stability was demonstrated to allow appropriate shipping and handling of specimens. Clinically defined specimens were analyzed using receiver operator characteristic (ROC) analysis of the Aβ42/40 results with respect to β-amyloid status. Results produced an area under the curve (AUC) of 0.94 and a cutoff of 0.102. This cutoff produced a sensitivity and specificity of 96.0 and 86.7%, respectively, and is consistent with the manufacturer proposed cutoff³. Furthermore, the AUC observed for the existing commercial assays was ≤ 0.89.

Conclusions Measurement of Aβ42/40 in patient plasma samples using a high efficiency platform is now available to assist physicians with identifying patients with β-amyloid plaques and potentially the presence of Alzheimer’s disease.

Authors/Disclosures
Ayla B. Harris (Labcorp) PRESENTER	No disclosure on file
Tien T. Le (Labcorp)	No disclosure on file
Bradley Collier (Labcorp)	No disclosure on file
Matthew Chappell (Labcorp)	No disclosure on file
Ahmed Chenna, PhD (Monogram Biosciences Inc)	Dr. Chenna has received personal compensation for serving as an employee of LabCorp-monogram Biosciences.
Youssouf Badal	No disclosure on file
Bryan Lim	No disclosure on file
Brandon Yee (Monogram Biosciences/LabCorp)	No disclosure on file
Christos J. Petropoulos, PhD (Monogram Biosciences, LabCorp)	Dr. Petropoulos has received personal compensation for serving as an employee of Monogram Biosciences-Labcorp. Dr. Petropoulos has received stock or an ownership interest from Laboratory Corporation of America Holdings. Dr. Petropoulos has received intellectual property interests from a discovery or technology relating to health care.
John Winslow, PhD (Monogram Biosciences Inc., Laboratory Corporation of America)	Dr. Winslow has received personal compensation for serving as an employee of Monogram Biosciences/Labcorp. Dr. Winslow has stock in Labcorp. Dr. Winslow has received intellectual property interests from a discovery or technology relating to health care.
Deborah Boles	No disclosure on file
Russell Grant (labcorp)	No disclosure on file