Working group Clinical Neurochemistry (AG Tumani)

Applying biomarkers as objective readout measures in clinical trials or to improve early (differential) diagnosis and enable prediction of disease progression is a major research focus of our working group. For that reason, we have a special interest in brain-derived markers that represent specific pathological processes in the central nervous system. One such marker, indicating axonal damage are neurofilaments. We already incorporated neurofilament proteins into our routine analysis for the differential diagnosis of ALS (more information can be found in the section “Routine analysis” and on the homepage of our CSF laboratory

(https://www.uniklinik-ulm.de/neurologie/laboratorien/liquorlabor.html).

However, as there are still open questions regarding the use of neurofilament analysis in other neurological diseases, we investigate their potential as biomarkers for prognosis or disease monitoring. Another marker we are interested in, representing astrocytic damage, is the Glial acidic fibrillary protein (GFAP). GFAP is found to be elevated e.g., in blood of AD patients and seems to be a disease progression marker in MS. Furthermore, we also work on synaptic proteins such as beta-synuclein or SNAP-25 which could enable an early diagnosis of neurological diseases as synaptic deterioration occurs early in the disease course of many neurological diseases.

In the Neuro-Biobank with a focus on neurodegenerative (ALS, dementia, Parkinson's) and inflammatory (multiple sclerosis, neuroborreliosis, acute meningoencephalitis) diseases biological samples are preserved with the approval of the ethics committee and the patients’ consent. The standardized biobanking mainly focuses on CSF, serum, and plasma samples and is extended to other biomaterials such as urine, tears, skin, and DNA in the context of specific research questions. The samples are utilized to assess the clinical relevance of new diagnostic tests, in biomarker projects, as well as in scientific collaborations.

We work in close collaboration and proximity to the routine laboratory for CSF diagnostics. The laboratory for CSF diagnostics and clinical neurochemistry is one of the training laboratories certified by the German Society for CSF diagnostics and clinical neurochemistry (DGLN) and is accredited by the German Accreditation Body (DAkkS). Patient samples from the in- and outpatient units of the department of Neurology of the University Hospital Ulm as well as from external senders are analyzed. The laboratory for CSF diagnostics offers a broad spectrum of parameters, covering all methods of routine CSF analysis as outlined in the S1 guidelines on lumbar puncture and cerebrospinal fluid analysis (https://doi.org/10.1186/s42466-020-0051-z) as well as an extensive spectrum of special parameters. New developments that were integrated into the spectrum of methods in the recent years include dementia markers (pTau, amyloid-beta ratio) for degenerative CNS diseases, CXCL13 and free (kappa/lambda) immunoglobulin light chains for inflammatory CNS diseases, as well as autoimmune-antibody diagnostics for paraneoplastic syndromes, autoimmune encephalitis, and NMOSD/MOG-AD. For more information on the currently offered parameters of CSF analysis please visit the homepage of the CSF laboratory (https://www.uniklinik-ulm.de/neurologie/laboratorien/liquorlabor.html).

In addition to routine services, we also analyze the neurofilament light (NfL) chains in serum and phosphorylated neurofilament heavy (pNfH) chains in CSF on a weekly basis in our routine laboratory. Hereby we established cut-offs for the differential diagnosis of ALS. More information and the requisition slip can be found on the homepage from our CSF laboratory (https://www.uniklinik-ulm.de/neurologie/laboratorien/liquorlabor.html).

We belong to national and international networks of specialized centers and are involved in the collection of biomaterials to build up large bio-depositories to enable research focused on the spectrum of neurodegenerative diseases which are often very rare.

Our group initiated the German Research Consortium of frontotemporal lobar degeneration to develop and evaluate parameters which help clinicians to diagnose FTLD at an early stage and follow its progression, with the overall aim to develop effective objective targets for therapeutic strategies (www.ftld.de). As this was successful, we have now started clinical trials in FTLD, investigating an active immunotherapy directed against pathologically modified tau protein that is the main constituent of pathological changes in nonfluent variant of PPA.

An important point for the implementation of fluid biomarkers into clinical routine is the standardization of sample collection, processing and storage. We are involved in several international networks with the aim to advance standardization in CSF analysis (BiomarkAPD, SOPHIA, CSF Society, KKNMS) and regularly provide workshops on basic knowledge to work with CSF.