The Relationship between Different Assays for Detection and Quantification of Amyloid Beta 42 in Human Cerebrospinal Fluid

Teresa A Ellis,Jinhe Li,Jeffrey F Waring,David Leblond

doi:10.1155/2012/984746

Abstract

Alzheimer's disease (AD), which is characterized by a degeneration of neurons and their synapses, is one of the most common forms of dementia. CSF levels of amyloid β 42 (Aβ 42) have been recognized as a strong candidate to serve as an AD biomarker. There are a number of commercial assays that are routinely employed for measuring Aβ 42; however, these assays give diverse ranges for the absolute levels of CSF Aβ 42. In order to employ CSF Aβ 42 as a biomarker across multiple laboratories, studies need to be performed to understand the relationship between the different platforms. We have analyzed CSF samples from both diseased and nondiseased subjects with two different widely used assay platforms. The results showed that different values for the levels of CSF Aβ 42 were reported, depending on the assay used. Nonetheless, both assays clearly demonstrated statistically significant differences in the levels of Aβ 42 in CSF from AD relative to age-matched controls (AMC). This paper provides essential data for establishing the relationship between these assays and provides an important step towards the validation of Aβ 42 as a biomarker for AD.

Highlights

Alzheimer’s disease (AD) is the most common neurodegenerative disorder
The Aβ1−42 ELISA standard curve showed a dynamic range of 125 to 2000 pg/mL, with an limit of detection (LOD) of 50 pg/mL, and the average CV based on sample duplicates was 3.9%
The Aβx−42 ECL assay standard curve showed a dynamic range of 12 to 3000 pg/mL, with an LOD of approximately 20 pg/mL, and the average CV based on sample duplicates was 7.1%

Summary

Introduction

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Because the disease is often difficult to detect and diagnose at an early stage, a tremendous need exists for the identification and characterization of biomarkers that can be used to diagnose early-stage AD, or for monitoring new therapies for AD in clinical trials. Much interest has been generated regarding the use of CSF Aβ42 as a biomarker for diagnosing and tracking AD progression [1, 2]. Several different commercially available assays for measuring Aβ42 are currently employed across laboratories. These assays give diverse values for the levels of CSF Aβ42 [3, 4]. The relationships between the reported CSF Aβ42 values from these different assays are unclear, but researchers agree in the importance of standardizing assays for CSF Aβ42 [4]

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Discussion

Conclusion