Neurodegenerative diseases are incurable conditions that result in neuronal dysfunction and cell death. The immune system plays an important role in central nervous system (CNS) homeostasis and impaired immune function may contribute to neurodegenerative diseases. In particular, misguided activation of microglia, the resident tissue macrophages of the CNS, may disturb neural function and promote degeneration.
The interdisciplinary team led by Josef Priller consists of neurologists, psychiatrists and neuropsychologists who share an interest in neurodegenerative diseases, in particular Alzheimer’s disease (AD), Huntington’s disease (HD) and frontotemporal lobar degeneration (FTLD). The team has been successfully conducting industry-sponsored phase 1 to phase 3 studies and has coordinated investigator-initiated trials into potential neuroprotective drugs, such as green tea ECGC. Drawing on a longstanding expertise in neuropsychiatry, the team has been investigating behavioural and psychological symptoms of dementia and was instrumental in formulating clinical guidelines.
In order to study mechanisms of disease, the laboratory team has been immunophenotyping myeloid cells from blood and CNS using state-of-the-art techniques like RNA sequencing and mass cytometry. In a translational approach, repurposing of licensed drugs that modulate the proteostasis network has been explored in preclinical models of disease. Moreover, patient-derived pluripotent stem cells have been generated in order to study the effects of genetic and environmental disturbances on the pathogenesis of neurodegenerative diseases and to screen for potential disease-modifying drugs.
As one of the major clinical centers contributing to this longitudinal study on cognitive impairment and dementia, we have been seeking to improve the detection of the early disease stages of AD. In a substudy, we have been trying to correlate olfactory function with cognitive measures and hippocampal volume in patients with subjective cognitive decline, mild cognitive impairment and AD. In another substudy, we have been exploring the role of myeloid cells in AD and the potential to use bioenergetic dysfunction of mononuclear cells as a biomarker of disease progression in AD and FTLD.
In this longitudinal study on behavioural variant frontotemporal dementia and primary progressive aphasias, we have been trying to provide a better understanding of the pathogenesis and the disease course of FTLD.