The European Medicines Agency EMA defines a biomarker as a biological molecule found in blood, other body fluids, or tissues that can be used to follow body processes and diseases in humans and animals. So far, the vast majority of biomarker in clinical use are related to cancer and cardiovascular disease, while the marker-based assessment of psychiatric diseases is still a new field – in particular since biomarker are preferentially measured in blood, whereas the pathological processes happen in the brain. The target structures of our research are proteins, which we systematically identify and quantify in blood or cerebrospinal fluid with the help of modern mass spectrometry-based approaches (aka Proteomics). According to the principle ‘from mouse to man’, we build on our experience in the proteomic phenotyping of mouse models of neuropsychiatric relevance for that purpose. With these approaches, we not only aim to improve the options for diagnosis and prognosis of psychiatric diseases, but also to gain insights into the molecular mechanisms underlying the pathological processes.
Overarching goals
When considering the prerequisites for successful molecular biomarker research in general, and for the identification of meaningful protein signatures in particular, the quality of the sample material under study is at least as important as the analytical approach applied. In close collaboration with the responsible clinical colleagues, we will thus mainly make use of the growing departmental biomaterial bank for future proteomic studies in the framework of research questions related to different psychiatric diseases.
Another field of application of mass spectrometry in neurodegeneration research is the molecular characterization of beta-amyloid peptides, which play a role in the etiology of Alzheimer dementia. Apart from chemically or post-translationally modified species, we are particularly interested in the characterization of N-terminally elongated or truncated beta-amyloid peptides. Relative concentration changes (i.e. peptide ratios) of some of these variants were recently described as promising biomarker candidates for the diagnosis of Alzheimer dementia and we thus pursue if the specific detection of distinct peptide species may have further potential in this direction.
As immunoprecipitation of beta-amyloid peptides is a key step in the sample preparation for such experiments, we are also engaged in the development and characterization of antibodies, which can recognize particular peptide features.
Selection of current projects and collaborations
- Further development of our technology platform for proteomic phenotyping of mouse models toward applications to patient material
- Characterization of N-terminally elongated Aβ(-3-x) or truncated Aβ(4-x)/Aβ(5-x) beta-amyloid peptides: identity, occurrence, and mechanisms of formation (with Dr. Hans Klafki und Prof. Dr. Oliver Wirths, UMG Psychiatrie)
- Mapping the recognition sites of antibodies specific for beta-amyloid peptides (with Dr. Hans Michael Maric, Rudolf-Virchow-Zentrum Würzburg)
Selected publications
- Chatterjee, M.; Özdemir, S.; Kunadt, M.; Koel-Simmelink, M.; Boiten, W.; Piepkorn, L.; Pham, T.V.; Chiasserini, D.; Piersma, S.R.; Knol, J.C.; Möbius, W.; Mollenhauer, B.; van der Flier, W.M.; Jimenez, C.R.; Teunissen, C.E.; *Jahn, O.; Schneider, A. C1q is increased in cerebrospinal fluid-derived extracellular vesicles in Alzheimer’s disease: A multi-cohort proteomics and immuno-assay validation study. Alzheimer’s & Dementia 2023; 19:4828-484013066 (*co-senior author)
- Liepold, T.; Klafki, H.W.; Kumar, S.; Walter, J.; Wirths, O.; Wiltfang, J.; Jahn, O. Matrix development for the detection of phosphorylated Amyloid-β peptides by MALDI-TOF-MS. Journal of the American Society for Mass Spectrometry 2023; 34:505-512
- Klafki, H.W.; Wirths, O.; Mollenhauer, B.; Liepold, T.; Rieper, P.; Esselmann, H.; Vogelgsang, J.; Wiltfang, J.; Jahn, O. Detection and quantification of Aβ−3–40 (APP669-711) in cerebrospinal fluid. Journal of Neurochemistry 2022; 160:578-589
Contact
Research Group Leader
Prof. Dr. Olaf Jahn
+49 551 3962007 / +49 551 20131313
olaf.jahn(at)med.uni-goettingen.de
Technical assistance / Programming
Lars Piepkorn
+49 551 3962007
lars.piepkorn(at)med.uni-goettingen.de