Frontotemporal lobar degeneration (FTLD) is a general cause of frontotemporal dementias (FTDs) which are after Alzheimer's disease (AD) and dementia with Lewy bodies the third most common dementia across all age groups. FTD is often associated with movement disorders such as parkinsonism or motor neuron disease (MND). Subtypes are characterized by abnormal deposition of protein aggregates of the microtubule-associated protein tau (MAPT), TAR-DNA-binding protein 43 (TDP-43) or fused-in-sarcoma/translocated in liposarcoma (FUS) or proteins of the ubiquitin-proteasome system (UPS). The majority of the tau-negative familial cases are positive for ubiquitinated inclusions of TDP-43 which is prevalent also in Amyotrophic Lateral Sclerosis (ALS). We have been generating mouse models for several FTD and ALS genes. By focusing on specific embryonic and adult phenotypes, we apply transcriptome analysis in order to determine the pathways and genes, that are misregulated in the presence of ALS/FTD mutations.

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