Irina Alafuzoff, Sweden
Akademiska sjukhuset Klinisk patologiAuthor Of 1 Presentation
ACCUMULATION OF ALPHA-SYNUCLEIN WITHIN THE LIVER: A POTENTIAL FEATURE IN THE PATHOGENESIS OF PARKINSON’S DISEASE AND RELATED SYNUCLEINOPATHIES
Abstract
Aims
The aim of this study is to investigate whether the liver is susceptible to α-syn accumulation in Parkinson’s disease (PD).
Methods
We assessed whether α-syn assemblies could be internalized by cultured primary human and HuH-7 hepatocytes. We then characterized human α-syn in liver tissue samples from transgenic models modeling PD, multiple system atrophy and Alzheimer’s disease (AD). Finally, we corroborated our results in human PD using imaging techniques.
Results
We demonstrate that human hepatocytes internalize oligomeric α-syn assemblies mediated, at least in part, by the gap junction protein connexin 32 (Cx32). Moreover, we identified a time dependent accumulation of α-syn pathology within the liver of three different transgenic mouse models overexpressing human α-syn under CNS-specific promoters. Such a brain to liver transmission route could be corroborated by detection of α-syn pathology within the liver of wild type mice one-month after a striatal α-syn injection. Notably, accumulation of Aß pathology in mice modeling AD was relatively absent. Consistent with our models, we identified the presence of α-syn pathology in a subset of human liver tissues from cases neuropathologically diagnosed with α-syn in the brain.
Conclusions
Our preliminary observations reveal α-syn pathology accumulation within the liver in a subset of human PD cases and mice modeling PD, a pathological process unique tothe synucleinopathies as pathology associated with AD is relatively absent. These results suggest that α-syn liver accumulation is likely a consequence of brain to liver or peripheral-liver transmission. Thus, the liver may be involved in the clearance and detoxification of pathological proteins in PD and related synucleinopathies.