Characterizing the expression profile of 3R tau pathology in Pick’s disease
Pick's disease (PiD) is a rare neurodegenerative disorder defined by dementia, frontotemporal lobe atrophy, and 3-repeat tau inclusions. To elucidate PiD pathobiology, we performed the first bulk transcriptomics study on PiD using short- and long-read sequencing on the parietal cortex of 28 PiD and 15 control samples. We identified several significantly differentially expressed genes, with <i>CCL2</i> displaying the strongest association with 3-repeat tau pathology and increased burden in PiD compared to those in 4-repeat tau progressive supranuclear palsy (PSP) cases. Investigation of co-expressed genes and pathways suggested the involvement of mRNA processing, mitochondrial function, and immune processes in disease pathobiology. Long-read RNA sequencing on a subset of samples (eight PiD and four control) proposed novel, potentially disease-associated transcripts for <i>AZGP1</i>, <i>CD44</i>, <i>HSD11B2</i>, and <i>WIF1</i>, predicted to result in truncated proteins. In conclusion, we observed transcriptomic changes in the parietal cortex of patients with PiD that may inform into clinically relevant biomarkers and therapeutic strategies.
Authors
- Monica Castanedes‐Casey (ORCID: https://orcid.org/0000-0002-8441-7801)
- Nicole Tamvaka (ORCID: https://orcid.org/0009-0002-9748-8526)
- Delaney Liskey
- Keith A. Josephs (ORCID: https://orcid.org/0000-0003-2930-8634)
- Dennis W. Dickson (ORCID: https://orcid.org/0000-0001-7189-7917)
- Caroline Graff (ORCID: https://orcid.org/0000-0002-9949-2951)
- Zbigniew K. Wszołek (ORCID: https://orcid.org/0000-0001-5487-1053)
- Michael G. Heckman (ORCID: https://orcid.org/0000-0003-3770-9331)
- Melissa E. Murray (ORCID: https://orcid.org/0000-0001-7379-2545)
- Marios Gavrielatos (ORCID: https://orcid.org/0000-0002-6052-5517)
- Shanu F. Roemer (ORCID: https://orcid.org/0000-0002-3597-1400)
- Bradley F. Boeve (ORCID: https://orcid.org/0000-0002-4153-8187)
- Alexandra I. Soto‐Beasley (ORCID: https://orcid.org/0000-0002-0153-1917)
- Owen A. Ross (ORCID: https://orcid.org/0000-0003-4813-756X)
- Marka van Blitterswijk (ORCID: https://orcid.org/0000-0002-3054-7053)
- Zachary Quicksall (ORCID: https://orcid.org/0000-0002-8791-0925)
- Yingxue Ren (ORCID: https://orcid.org/0000-0003-4529-5722)
- Evan Udine
Institutions
- Mayo Clinic (US)
- WinnMed (US)
- Mayo Clinic in Florida (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-05-02
- DOI
- https://doi.org/10.1126/sciadv.adt6105
- Citations
- 2
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 2.33