Amyloid β peptides are differentially vulnerable to preanalytical surface exposure, an effect incompletely mitigated by the use of ratios

Introduction: We tested the hypothesis that the amyloid β (Aβ) peptide ratios are more stable than Aβ₄₂ alone when biofluids are exposed to two preanalytical conditions known to modify measurable Aβ concentration.

Methods: Human cerebrospinal fluid (CSF) and culture media (CM) from human cortical neurons were exposed to a series of volumes and polypropylene surfaces. Aβ₄₂, Aβ₄₀, and Aβ₃₈ peptide concentrations were measured using a multiplexed electrochemiluminescence immunoassay. Data were analyzed using mixed models in R.

Results: Decrease of measurable Aβ peptide concentrations was exaggerated in longer peptides, affecting the Aβ₄₂:Aβ₄₀ and Aβ₄₂:Aβ₃₈ ratios. However, the effect size of surface treatment was reduced in Aβ peptide ratios versus Aβ₄₂ alone. For Aβ₄₂:Aβ₄₀, the effect was reduced by approximately 50% (volume) and 75% (transfer) as compared to Aβ₄₂ alone.

Discussion: Use of Aβ ratios, in conjunction with concentrations, may mitigate confounding factors and assist the clinical diagnostic process for Alzheimer's disease.