Regional Volumes
Brain volumes in various cortical and subcortical regions at Baseline and Weeks 8, 12, and 16 (t0, t8, t12, and 16, respectively) post-inoculation. Note the progressive brain atrophy in regions of accumulating synuclein burden (piriform cortex, entorhinal cortex, hippocampus), which have direct or higher order connections to the AON. There is no volumetric change in regions without synuclein pathology (e.g. thalamus). * p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001
Cortical Thickness
Cortical thinning with disease progression.
Spatiotemporal pattern of cortical thinning. The colder colors (blue and purple) represent greater cortical thinning. * p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001
We have been able to show highly significant brain atrophy in this model. Regional brain atrophy is a well-established imaging biomarker in human Parkinson's disease. The Anterior Olfactory Nucleus (AON), piriform cortex, and entorhinal cortex show early and progressive atrophy in the ipsilateral hemisphere. We see late changes in the hippocampus and contralateral piriform and entorhinal regions, which reflect the spread of synuclein to these higher-order structures. Note that we do not see atrophy in regions without synuclein pathology, such as the thalamus.
In this AON model, the cortical thickness measures are extremely sensitive, with highly significant thinning seen in the piriform and entorhinal cortices. The cortical surface maps nicely demonstrate the spatiotemporal pattern of cortical thinning, which follows the spread of synuclein pathology. In these maps, the blue and purple colors represent thinner cortex which starts in the ipsilateral piriform cortex and then becomes more extensive and severe. This thinning then progresses to the contralateral piriform cortex between 12-16 weeks post-inoculation.