Global Biomarker Standardization Consortium (GBSC)

Overview

The Alzheimer's Association® established the Global Biomarker Standardization Consortium (GBSC) over a decade ago to gather key researchers, clinicians, industry, regulatory and government leaders in Alzheimer's disease and dementias to achieve consensus on the best ways to standardize and validate biomarker tests for use in global clinical practices.

In the past few years, the Alzheimer's and dementia field has developed improved techniques and technologies aimed at early diagnosis and detection of Alzheimer's disease and related dementias. The field has seen remarkable growth in research using clinical assessments, psychometric testing, cerebrospinal fluid (CSF) and blood-based biomarkers, magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging of the brain to detect hallmarks of neurodegenerative diseases at its earliest stages. Before these and other diagnostic measures can be incorporated into clinical practice worldwide, they must be standardized and validated on a global scale. The GBSC convenes these experts to address the challenges inherent in this goal and to develop global standards required for worldwide implementation.

The GBSC welcomes new members who are aligned in its commitment to research and innovation. The current leadership includes Dr. Maria Carrillo (Alzheimer’s Association); Dr. Charlotte Teunissen (Amsterdam UMC); Dr. Henrik Zetterberg (University of Gothenburg); and Dr. Kaj Blennow (University of Gothenburg).

Initiatives

Quality Control (QC) Program

Widely available, exact, reliable and stable biomarker measurements would serve as the basis for a more general use of fluid biomarkers in clinical diagnostic routine. To this end, the Alzheimer’s Association launched its Quality Control (QC) Program in 2009 that brings together laboratories across the globe with the aim of standardizing the measurement of potential Alzheimer's biomarkers. This program started with the aim to establish a tool to monitor the performance of cerebrospinal fluid (CSF) biomarker measurements between clinical and large research laboratories using currently available testing platforms such as mass spectrometry and immunoassays. The expanded long-term goal of the program is to improve the quality of the entire chain of procedures associated with fluid biomarker measurements, both CSF and blood, which would stabilize results over time and harmonize biomarker values between laboratories worldwide.

Today, more than 90 laboratories in North and South America, Asia, Australia and Europe are active members and participate in the QC Program.

Through the QC Program’s associated projects, the team has identified multiple factors in biofluid testing that can contribute to variability in results, including manual steps required as part of standard testing procedures, and inherent characteristics of plate-based tests (variability in coating procedures, preparation of the calibration curve, etc.). As a result, dramatic improvements in testing performance have been made with new fully automated instruments, and the program will continue to monitor and improve the performance of these diagnostic assays.

Reference Materials Program

The Alzheimer’s Association Reference Materials working group addresses issues associated with developing a universal material for fluid biomarkers. This provides a basis for standardized measures and calibration of instruments worldwide. The group drives consensus on the need for new reference materials, investigates the appropriate material to use for calibration and defines the role for internal control samples. This has been done for other similar biomarker tests, such as cholesterol, to standardize measures on a global scale. A certified reference material for Aβ 42 was established for cerebrospinal fluid in collaboration with the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and is currently commercially available via the Joint Research Centre.

Reference Methods Program

The Alzheimer’s Association Reference Methods working group focuses on developing reference method definitions for the ideal protocol. This will help determine an absolute quantification of peptides/proteins in fluid biomarkers. Some examples include using mass spectroscopy or immunoassay platforms for analyzing biomarkers. Reference methods have been developed for vitamins and hormones in other diseases; however, measurement of peptides and proteins such as amyloid beta or tau will need different reference methods to facilitate accurate testing results. The group addresses surrounding issues related to various methodologies and develops universal reference methods for use in various measures of fluids. Two reference methods for the protein Aβ 1-42 in cerebrospinal fluid (CSF) have been certified. Additional methods for other CSF proteins are currently being developed.

Cerebrospinal Fluid (CSF) Pre-Analytics Consortium

The Alzheimer’s Association CSF Pre-Analytics Consortium brings together academic and industry expertise in Alzheimer’s disease biomarkers and automated CSF diagnostics. This is a pre-competitive collaboration to standardize pre-analytical factors in CSF handling and processing. The goal of the consortium is to develop a pre-analytic protocol for fresh CSF sample collection that could be used in clinical practices to minimize the systemic differences in the biomarker measurements.

Standardization of Alzheimer’s Blood Biomarkers (SABB) Program

Launched in the summer of 2018, the Alzheimer’s Association SABB Program brings together expertise in fluid biomarkers from academic, government and industry partners across the globe. With research advancements and new technologies in development for blood biomarker testing for Alzheimer's disease, there is a need to standardize pre-analytical factors in blood sample collection, handling and processing. This working group has been tasked to objectively evaluate pre-analytical factors and to define consensus procedures for collection and processing of blood samples that would enable standardized measurement of Alzheimer's disease biomarkers in clinical use.

Meeting agendas and summaries

Related papers and abstracts

• Hansson O., Edelmayer, R.M., Boxer A.L, et al. (2022) The Alzheimer’s Association appropriate use recommendations for blood biomarkers in Alzheimer’s disease. Alzheimer's & Dementia. 00: 1–18.
• Hansson O., Batrla R., Brix B., et al. (2021) The Alzheimer's Association international guidelines for handling of cerebrospinal fluid for routine clinical measurements of amyloid β and tau. Alzheimer's & Dementia. 17: 1575– 1582. 
• Verberk I.M.W., Misdorp E.O., Koelewijn J., et al. (2021) Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease–related blood-based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group. Alzheimer's & Dementia. 00: 1- 14.
• Pannee J., Shaw L.M., Korecka M., et al. (2021) The global Alzheimer's Association round robin study on plasma amyloid β methods. Alzheimer's & Dementia. 13:e12242.
• Blennow K., Zetterberg H. (2018) Biomarkers for Alzheimer’s disease: current status and prospects for the future. Journal of Internal Medicine. Dec; 284(6): 643-663.
• Pannee J., Gobom J., Shaw LM., et al. (2016) Round robin test on quantification of amyloid‐beta 1‐42 in cerebrospinal fluid by mass spectrometry. Alzheimer's & Dementia. 12: 55-9.
• Vandijck M., Moonen R., Andreasson U., et al. (2015) Correlation of the modified innotest β-amyloid 1-42 with a lc-ms/ms candidate reference method. Alzheimer's & Dementia. (2015) 11 (7), P385.
• Leinenbach A., Pannee J., Dülffer T., et al. (2014) Mass Spectrometry-Based Candidate Reference Measurement Procedure for Quantification of Amyloid-β in Cerebrospinal. Clinical Chemistry.  
• Pannee J., Portelius E., Minthon L., et al. (2014) Reference measurement procedure for CSF amyloid beta (Aβ) 1-42 and the CSF Aβ 1-42 /Aβ 1-40 ratio - a cross-validation study against amyloid PET. Journal of Neurochemistry. 139(4): 651-658.
• Korecka M., Waligorska T., Figurski M., et al. (2014) Qualification of a surrogate matrix-based absolute quantification method for amyloid-β 42 in human cerebrospinal fluid using 2D UPLC-tandem mass spectrometry. Journal of Alzheimer’s Disease. 41(2): 441-51.
• Carrillo M., Blennow K., Soares H., et al. (2013) Global standardization measurement of cerebral spinal fluid for Alzheimer's disease: An update from the Alzheimer's Association Global Biomarkers Consortium. Alzheimer’s & Dementia. 9(2): 137-140.
• Mattsson N., Andreasson U., Persson S., et al. (2013) CSF biomarker variability in the Alzheimer's Association quality control program. Alzheimer's & Dementia. 9: 251-61.
• Mattsson N., Andreasson U., Carrillo M., et al. (2012) Proficiency testing programs for Alzheimer’s disease cerebrospinal fluid biomarkers. Biomarkers in Medicine. Aug; 6(4): 401-7.  
• Mattsson N., Zegers I., Andreasson U., et al. (2012) Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β 42. Biomarkers in Medicine. Aug; 6(4): 409-17
• Mattsson N., Andreasson U., Persson S., et al. (2011) The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers. Alzheimer's & Dementia. Jul; 7/(4): 386-395 e6.
• Blennow K., Hampel H., Weiner M., et al. (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer's disease. Nature Review Neurology. Mar; 6(3): 131-44.

Events

GBSC Winter Webinar
December 20, 2022

Alzheimer's Association International Conference (AAIC)
Amsterdam, Netherlands and Online
July 16-20, 2023

More information

For investigators who are interested in more information on GBSC and its associated projects and events, please contact:

Christopher Weber, Ph.D.
Director, Global Science Initiatives
Alzheimer's Association
cweber@alz.org