A Consensus in Korea Regarding a Protocol to Reduce Preanalytical Sources of Variability in the Measurement of the Cerebrospinal Fluid Biomarkers of Alzheimer's Disease

Cerebrospinal fluid (CSF) can provide vital informative about pathological processes occurring in the brain. In particular, the CSF concentrations of A beta 42, tTau, and pTau181 are useful for the early diagnosis of Alzheimer's disease (AD). However, many studies have demonstrated that confounding factors related to the preanalytical processing of CSF can seriously influence measurements of these AD biomarkers. It is therefore important to develop a standardized protocol for the acquisition and handling of CSF, particularly with regard to the types of tube used for collection and storage, the proper aliquot volume, blood contamination, and the number of tube transfers and freeze-thaw cycles, because these aspects of the procedure have been shown to affect AD biomarker measurements. A survey of the impact of several individual preanalytical procedures on the measurement of AD biomarkers in CSF was conducted for this review article, and the implications of the differences among them are discussed. Furthermore, following a review of the procedures used in Korean and international biomarker laboratories, a consensus was reached among a cooperative Korean multicenter research group regarding a standardized protocol for the analysis of AD biomarkers in CSF. All efforts were made to be stringent regarding the controversial issues associated with this protocol, thus minimizing the confounding influence of various factors on current investigations using established AD biomarkers and on future studies using novel biomarkers of AD and other neurodegenerative disorders.