Pre‐analytical protocol for measuring Alzheimer's disease biomarkers in fresh CSF

Abstract

Abstract Introduction We aimed to establish a standardized, routine‐use pre‐analytical protocol for measuring Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF). Methods The effect of pre‐analytical factors (sample collection/handling/storage/transportation) on biomarker levels was assessed using freshly collected CSF. Tube type/sterilization was assessed using previously frozen samples. A low‐bind false‐bottom tube (FBT, Sarstedt) was used for all experiments, except tube types/sterilization experiments. Biomarkers were measured using Elecsys CSF assays. Results Amyloid beta (Aβ)1‐42 levels varied by tube type, using a low‐bind FBT reduced variation. Aβ1‐42 levels were higher with no mixing versus roller/inversion mixing. Aβ1‐42 levels were lower with horizontal versus upright transportation; this was resolved by maximal tube filling and storage at 2°C to 8°C. Aβ1‐40 levels were less strongly affected. Phospho‐tau and total‐tau levels were largely unaffected. Discussion We propose an easy‐to‐use, standardized, routine‐use pre‐analytical protocol, using low‐bind FBTs, for measuring AD CSF biomarkers in clinical practice.

Keywords

• Alzheimer's disease
• amyloid beta
• biomarker
• cerebrospinal fluid
• diagnosis
• pre‐analytical