Figure from Blumenstock et al., Acta Neuropathol 2019

Synaptic failure is believed to be an important cause of dementia in neurodegenerative diseases like Alzheimer`s disease. Also in Synucleinopathies (including Parkinson`s disease), dementia develops in a high number of patients. Due to incredible compensation capacity of the human brain, dementia however only become evident when more than half of all synapses are irreversibly lost. Here we aim at understanding early changes in synapse cellular and molecular functions in a mouse model of synucleinopathy. We aim to identify synapse protein changes that alter synaptic function due to the aggregation of the synaptic protein a-synuclein. We intend to discover new synaptic targets for a preventive therapeutical intervention in order to stop synapse loss in time and to identify patients with Parkinsons`s disease at risk to develop dementia early on.

We also propose to study the neoformed dopaminergic synapses from neurons grafted into the substantia nigra pars of mice. In particular, we will study how grafts form synapses with their targets in comparison with the synaptome of dopaminergic neurons from control mice. This data will be valuable for refining grafting techniques and establishing these approaches in human cell therapies of synucleinopathies.