Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview
Authors: Delaby Constance , Teunissen Charlotte E. , Blennow Kaj , Alcolea Daniel , Arisi Ivan , Amar Elodie Bouaziz , Beaume Anne , Bedel Aurélie , Bellomo Giovanni , Bigot‐Corbel Edith , Bjerke Maria , Blanc Marie‐Céline , Boada Mercè , Bousiges Olivier , Chapman Miles D , DeMarco Mari L. , D'Onofrio Mara , Dumurgier Julien , Dufour‐Rainfray Diane , Engelborgs Sebastiaan , Esselmann Hermann , Fogli Anne , Gabelle Audrey , Galloni Elisabetta , Gondolf Clémentine , Grandhomme Frédérique , Grau‐Rivera Oriol , Hart Melanie , Ikeuchi Takeshi , Jeromin Andreas , Kasuga Kensaku , Keshavan Ashvini , Khalil Michael , Koertvelyessy Peter , Kulczynska‐Przybik Agnieszka , Laplanche Jean‐Louis , Lewczuk Piotr , Li Qiao‐Xin , Lleó Alberto , Malaplate Catherine , Marquié Marta , Masters Colin L. , Mroszko Barbara , Nogueira Léonor , Orellana Adelina , Otto Markus , Oudart Jean‐Baptiste , Paquet Claire , Paoletti Federico Paolini , Parnetti Lucilla , Perret‐Liaudet Armand , Poec’h Katell , Poesen Koen , Puig‐Pijoan Albert , Quadrio Isabelle , Quillard‐Muraine Muriel , Rucheton Benoit , Schraen Susanna , Schott Jonathan M , Shaw Leslie M. , Suarez‐Calvet Marc , Tsolaki Magda , Tumani Hayrettin , Udeh‐Momoh Chinedu T. , Vaudran Lucie , Verbeek Marcel M. , Verde Federico , Vermunt Lisa , Vogelgsang Jonathan , Wiltfang Jens , Zetterberg Henrik , Lehmann Sylvain 
Published: December 2021

Background

The quantification of cerebrospinal fluid (CSF) biomarkers (Amyloid beta peptides [Aß1‐40 and Aß1‐42], t‐tau and p‐tau(181)) is progressively implemented in specialized laboratories as an aid for the multidisciplinary diagnosis of Alzheimer’s disease (AD). There is however a diversity of practices between centers related to pre‐analytical and analytical conditions, the calculation of ratios between analytes, the applied cut‐off, or the use of interpretation scales. Finally, for the same biochemical profile, the interpretation and reporting of results may differ from one center to another, which may raise questions about the commutability of the tests. So far, no consensus has been reached between the different laboratories involved to define the most appropriate conclusions/comments based on the profile of the quantified biomarkers.

This work is an essential step towards a consensual harmonization of clinical reporting after CSF analysis in the context of AD diagnosis, as advocated by the "Biofluid Based Biomarkers PIA" working group of the Alzheimer's Association.

Method

We obtained, by means of a questionnaire, a description of the pre‐analytical and analytical protocols and examples of reporting from 40 centers located in 15 countries, i.e. in the majority of countries that have implemented clinical CSF tests for the diagnosis of AD. We then adopted a consensus approach to propose harmonized comments corresponding to different AD CSF biomarker profiles observed in patients.

Result

Pre‐analytical procedures were very similar, among the centers. Regarding the analytical part, more than 88% of the laboratories use automatized immunoassays and more than 83% measure Aß1‐40 and compute the Aß1‐42/Aß1‐40 ratio, in addition to the three core biomarkers (Aß1‐42, t‐tau and p‐tau(181)). The cut‐off values of biomarkers used by the different laboratories are widely dispersed. Delay before sending back the results is lower than 1 week in more than 34% of the laboratories.

Conclusion

Our results highlight the state of the art in terms of clinical CSF analysis in the context of AD. Harmonization of clinical reporting between different centers could benefit AD care, prevention and treatment strategies, as a common terminology will allow a better assessment of the prevalence of AD and the contribution of biochemical biomarkers to its diagnosis.