Standardization and harmonization of a biomarker-based work-up for Alzheimer's disease

Date: 5 October 2017

Venue: Promotiezaal (UAntwerp, Campus Drie Eiken, Building Q) - Universiteitsplein 1 - 2610 Wilrijk (Antwerp) (route: UAntwerpen, Campus Drie Eiken)

Time: 2:00 PM - 4:00 PM

PhD candidate: Ellis Niemantsverdriet

Principal investigator: Sebastiaan Engelborghs, Maria Bjerke

Short description: PhD defence Ellis Niemantsverdriet - Department of Biomedical Sciences


Over the years, the clinical diagnosis of Alzheimer’s disease (AD) has experienced an evolution from clinical exclusion criteria to a biomarker-based diagnosis. Thanks to major advances in biomarker-based research, it is now possible to detect AD-related changes in a preclinical stage and this creates an exceptional window for early diagnosis, treatment, and prevention strategies. In this PhD thesis we hypothesized that biomarkers need standardization and harmonization as a final step before entering daily clinical practice on large scale.

Cerebrospinal fluid (CSF) biomarkers act as a mirror of the brain’s metabolism and reflect brain pathology. CSF is collected by lumbar puncture (LP), an invasive procedure that can result in post-LP complications. Consensus guidelines for LP procedure were formulated and these recommendations will minimize post-LP complications as procedure-related risk factors are taken into account.

To date, three AD CSF biomarkers are integrated in the clinical diagnostic criteria for AD, namely Aβ1-42, T-tau, and P-tau181. The CSF biomarker concentrations can be affected by a combination of different factors and this can effect measurement variability. This variability was investigated as further acceptance and worldwide integration of these CSF biomarkers in routine clinical practice is necessary. In addition, the CSF Aβ1-42/Aβ1-40 ratio might be of value in AD research as we detected that the ratio reflects early changes in the disease process. This finding is of utmost importance for the biomarker-based diagnosis of AD as well as for the selection of subjects for clinical trials with potential disease-modifying therapies.

Structural brain imaging is also used to measure biomarkers. We used MSmetrix that uses clinical brain MRI scans in contrast to many other tools that use specialized brain scans. Structural brain imaging is non-invasive and will result in less post-procedure complications in contrast to the LP, however the technique is more expensive than an LP and the accessibility of scanners is limited. Nevertheless, structural brain imaging is a is available without performing secondary examinations, as this technique is used in diagnostic work-up for AD to exclude other brain diseases.

The past decade, a lot of progress has been made with regard to standardization and harmonization of existing biomarkers for AD. The standardization and harmonization is essential as this will lead to the ability to reduce/control variability of measurement methodologies and to improve the observations. Eventually, the standardization and harmonization efforts can lead to study comparisons and ease the transition from research into clinical trials/clinical practice.