Tau Missorting in AD—Causes and Consequences

During the development of Alzheimer’s dementia, multiple changes occur in brain cells, making the search for and treatment of underlying causes difficult. Therefore, a key goal of Alzheimer’s disease (AD) research is to identify early changes occurring long before cognitive deficits become apparent. One such event is the so-called “missorting” of tau protein, which normally is found in the axons of neurons, but which in AD accumulates in the ”wrong” compartments, the cell bodies and dendrites. This project aims to analyze the reasons for this pathological change and to find ways to prevent it. The mechanism of a second phenomenon in AD, the propagation of tau pathology between neurons, also is currently unclear. This propagation leads to the spread of tau neurofibrillary tangles from the transentorhinal regions of the brain to others, which Braak staging measures as a signifier of disease progression and which correlates with cognitive decline. The analysis of individual neuronal compartments observed via microfluidic devices we will perform in this project should provide evidence of whether tau propagation is caused by pathological signaling cascades or by the release and reuptake of pathological forms of tau between cells.