Tidiga indikatorer på nervsystemet dysfunktion i djurmodeller av Parkinsons sjukdom

Parkinson´s disease (PD) is characterized by pathological misfolding of the protein alphasynuclein (asyn), which causes progressive neurodegeneration in the brain and subsequent motor-symptoms.

We hypothesized that PD can be divided in two subtypes: (1) a body-first type, where damage to the cardiac and enteric nervous system precedes damage to the brain up to 20-years prior, and (2) a brain-first type where neuronal loss in the brain precedes nerve damage to other organs.

Here, we will emulate the two types of PD as observed in humans by injecting asyn pathology in the gut vs. in the amygdala of transgenic or wild-type mice.

We will map the spatio-temporal spread of asyn pathology and progressive neuronal dysfunction from the initiation via early disease stages to late disease stages using a battery of in vivo and ex vivo techniques such as longitudinal in vivo functional imaging, autoradiography, symptom scoring, and thorough immunohistochemical analysis.

Finally, we hypothesize that the phenotypic and histopathological variability between body-first and brain-first PD could result, apart from the different disease initiation site, from variation in intrinsic structure of the asyn aggregates.

To investigate this hypothesis, we will use a panel of thiophene-based ligands that produce a ‘spectral fingerprint’ of protein aggregates upon interaction.

This project may contribute significantly to the development of early disease biomarkers and disease-modifying treatment targets.