RNA Sequencing

To better understand the gene expression profile of Pick’s disease and 3R tau pathology the PIC is establishing RNA Sequencing efforts of Pick’s disease cases. By utilizing available RNA sequencing technologies, including bulk sequencing, single cell or single nuclei sequencing and long read isoform sequencing, we will be able to comprehensively describe the transcriptional changes that take place during the disease process at the gene, transcript, and cell-type level. We will complement that with pathway and network analyses to gain a better understanding into the biological effects of 3R tau aggregates in Pick’s disease, as well as dysregulated pathways and disease processes that could be leveraged in the future for modeling studies and ultimately, therapeutic development.

Spatial Transcriptomics

Very little is known about the composition of Pick bodies, as well as their interactions with their microenvironment and how they contribute to disease processes; is 3R tau aggregation in Pick bodies the pathogenic process of Pick’s disease that disrupts physiological cell function, or do Pick bodies start out to protect the cell by “collecting” all pathogenic tau species in one space to help with cell survival?
In an attempt to answer these questions, we plan on performing spatial transcriptomics studies on Pick’s disease cases. Spatial transcriptomics offers the unique advantage of characterizing gene expression while maintaining spatial resolution and thus providing novel insight into disease-relevant mechanisms and dysregulated cellular networks in the microenvironment of pathological tau aggregates. By focusing on the microenvironment of Pick bodies, we hope expand our current understanding of the relationship Pick bodies with the neurodegenerative process.

By integrating these transcriptomics approaches we hope to assist in therapeutic development; especially since the lack of tau-directed therapies continues to be a major challenge in the field.