Therese Koal (Presenter)
Biocrates Life Sciences AG
Bio: Therese Koal is as Head of R&D responsible for mass spectrometry-based kit design and product development at BIOCRATES Life Sciences AG. Standardization/harmonization of metabolomics, translational medicine, medical device development and clinical laboratory diagnostics, also belong to Dr. Koal's scope of activities and interest. Before she joined BIOCRATES in 2006, she worked at the Medical School of Hannover, Germany, where she developed one of the first MS/MS-based clinical routine platform for Therapeutic Drug Monitoring (TDM) of immunosuppressive and antiretroviral drugs in Germany. Dr. Koal earned her doctorate in analytical chemistry from the University of Leipzig, Germany, where she also completed a post-graduate study in toxicology. She has multitude of scientific publications/patents in the area of metabolomics, TDM, and is lecturer in academia for metabolomics.
Authorship: Therese Koal (1), Kristaps Klavins (1), Christian Humpel (2)
(1) Biocrates Life Sciences AG, Innsbruck, Austria, (2) Medical University Innsbruck, Innsbruck, Austria
| Short Abstract There is a strong need for pre-symptomatic biomarkers in Alzheimer´s disease (~20 years before manifestation) due to the very progressive disease character and the lack of therapy at current time point of diagnosis. Targeted metabolomics has the potential to improve the current diagnosis in cerebrospinal fluid (CSF) and use metabolic signatures as (early) disease detection in blood for population screening approach. Therefore, appropriate studies in CSF and blood were performed. In the result, SM could be indentified as potential markers in CSF and PC and lyso PC as metabolic signature in blood. Alteration of PC and lyso PC are linked to phospholipase A2 (PLA2) because PLA2 catalyze cleavage of fatty acids fron sn-2 position of phospholipids producing free fatty acids and lyso PC. Data will be presented and hypothesis of PC and lyso PC related to PLA2 will be discussed. |
Long Abstract
Introduction
Alzheimer’s disease (AD) is a progressive neurodegenerative disease of the brain that gradually leads to severe cognitive impairment. Currently, the diagnosis of AD within the clinical routine is based on a time consuming combination of psychological testing, imaging and the analysis of three well-established biomarkers in the cerebrospinal fluid (CSF). However, there is an important need to improve diagnostic performance by new and more selective and specific biomarkers in CSF. Furthermore, due to the invasive nature of CSF collection, blood biomarkers need to be found, to allow early screening and multiple analyses of patients.
Methods
The targeted quantitative metabolome analysis for one hundred CSF samples (n=50 AD, n=50 controls), and plasma samples from controls (n=35) and mild cognitive impairment (MCI) (n=33) and AD (n=43) patients were carried out. The targeted quantification of more than 180 metabolites, including 40 acyl carnitines, 21 amino acids, 19 proteinogenic amino acids, 15 sphingolipids and 90 glycerophospholipids were performed using the AbsoluteIDQ® p180 Kit (BIOCRATES Life Sciences).
Results
Our data show that sphingomyelin SM (d18:1/18:0) were significantly altered in the CSF of AD patients compared to controls. (1) It proved to be a specific (76%) and sensitive (66%) biomarker with a defined cut-off of 546 nM. Additionally, we found that different PC and lysoPC are altered in plasma of AD and MCI patients compared to healthy controls. Our data suggest that the ratio of PC aa C34:4 to lysoPC a C18:2, representing the pathophysiological changes of phosphatidylcholines, might be highly useful as a novel plasma biomarker to diagnose dementia with an accuracy of 82-85%. (2)
Conclusion
Alterations of metabolic signatures in AD obtained by targeted metabolomics analysis shows the potential in early diagnosis of AD.
References & Acknowledgements:
(1) Koal T., Klavins K. et al. J Alzheimer´s Disease 44 (2015) 1193-1201
(2) Klavins K., Koal T. et al. Alzheimer´s & Dementia: Diagnosis, Assessment & Disease Monitoring 1 (2015) 295-302
| Description | Y/N | Source |
| Grants | no | |
| Salary | yes | Biocrates Life Sciences AG |
| Board Member | no | |
| Stock | no | |
| Expenses | no |
IP Royalty: no
| Planning to mention or discuss specific products or technology of the company(ies) listed above: | yes |