MDD is a complex and highly heterogeneous disease and the underlying pathomechanisms are most likely multifactorial and not fully understood to date. Contactin-associated protein-like 4 (CNTNAP4) belongs to a subgroup of the neurexin superfamily and is expressed in the CNS in excitatory as well as inhibitory neurons and oligodendrocytes. In neurons, CNTNAP4 is localized presynaptically and contributes to cell adhesion and dopaminergic as well as GABA-ergic signal transmission. Previously, a proteomic analysis of cerebrospinal fluid of psychiatric patients detected changes in protein levels of MDD patients compared to healthy controls. Significantly reduced concentrations were found for eight proteins, one of them being CNTNAP4, making it a potential biomarker for MDD. We therefor aim to validate the biomarker applicability of the protein. Furthermore, CNTNAP4 deficiency has been reported to deteriorate PD phenotype in asyn models. We therefore also study the mode of action of CNTNAP4 deficiency on asyn aggregation in neuronal cultures and potential pathological consequences in neurons.

Elevated levels of serum Neurofilament light chain (NF-L) have already been detected in blood and CSF of pre-symptomatic and symptomatic ALS patients. This project aims at demonstrating this elevation in ALS in vivo models in conjunction with other cellular changes typical for the disease. We could previously demonstrate an age- and genotype-specific increase in TDP-43 models with reduced numbers of motoneurons as well as denervation of the neuromuscular endplates (NMJs). We want to understand why NF-L is released in the extracellular space and model this in neuronal cultures.