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

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. Aβ(1‐42) levels were higher with no mixing versus roller/inversion mixing. Aβ(1‐42) levels were lower with horizontal versus upright transportation; this was resolved by maximal tube filling and storage at 2°C to 8°C. Aβ(1‐40) 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.