Alzheimer’s disease (AD) is the most common cause of dementia, however, effective treatment or prevention of the disease is not available to date. The aim of our work is to identify early factors that drive the pathogenesis in sporadic AD. We employ different disease models and post-mortem brain material to investigate molecular pathways leading to AD pathology.
Protein homeostasis or proteostasis is of major importance for neuronal function and maintained by balancing protein synthesis, folding and degradation. Accumulation of aberrant proteins, Aβ and tau - ultimately deposited in plaques and tangles, respectively - is a key event in AD, reflecting a severe disturbance in the proteostasis. We study pathways leading to this disruption in proteostasis and how it may be employed for therapeutic intervention. The unfolded protein response (UPR) is a stress pathway that is activated in response to disturbed proteostasis. Our group published the hallmark papers about activation of the UPR as very early event in AD and other tauopathies and showed that it is functionally connected to AD pathology. Incapability to restore the proteostasis leads to prolonged activation of the UPR and neurodegeneration.
By characterizing the pathways involved, we aim to identify how the adaptive stress response may be employed for early diagnosis and intervention and how environmental and genetic factors increase risk at AD. In addition, we are investigating ways to restore the proteostatic balance via removal of the aberrant proteins in particular via degradation by the autophagy/lysosomal pathway.
Please check out our movie about Alzheimer and how we study the disease for non-scientists.