Progressive supranuclear palsy (PSP) is the most common frontotemporal lobar degeneration associated with tau pathology. The majority of patients with PSP can be accurately diagnosed antemortem due to a characteristic clinical syndrome; however, there are atypical clinicopathologic forms of PSP that can mimic Parkinson’s disease, frontotemporal dementia, progressive nonfluent aphasia and corticobasal syndrome. While rare pathogenic variants, common risk factors, and – more recently – rare risk-associated variants have been identified in PSP, a significant proportion of the heritability for neurodegenerative tauopathies and other frontotemporal lobar degenerations remains unexplained, strongly suggesting that additional genetic risk factors await discovery. We assembled PSP samples for whole-genome sequencing (WGS) of neuropathologically characterized PSP, with the majority coming from the Mayo Clinic in Jacksonville. Other major contributors were the University of Pennsylvania and University College London.

The SeqLab Core at the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Uniformed Services University of the Health Sciences (HJF/USU) conducted genomic sequencing of de-identified DNA samples.  Library preparation used the Illumina PCR-free DNA workflow on SeqLab automated Hamilton STAR liquid handling platforms. Clustered libraries were sequenced using the Illumina HiSeq X platform.  FASTQ data were generated and genomic variants called after quality control, alignment and calling performed on HAS 2.0 software algorithm. The Genome Center for Alzheimer’s Disease (GCAD), at the University of Pennsylvania, processed the sequence data using a standardized pipeline.

Giovanni Coppola, MD
University of California Los Angeles

Dennis Dickson, MD
Mayo Clinic Jacksonville

Gerard D. Schellenberg, PhD
University of Pennsylvania

Judith Steen, PhD
Boston Children’s Hospital

Li-San Wang, PhD
University of Pennsylvania



UG3NS104095 “Impact of Coding and Non-coding Variation in Progressive Supranuclear Palsy”

Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

For investigators using NIH, CurePSP and Tau Consortium PSP WGS data:

This project was funded by the NIH grant UG3NS104095 and supported by grants U54NS100693 and U54AG052427. Queen Square Brain Bank is supported by the Reta Lila Weston Institute for Neurological Studies and the Medical Research Council UK. The Mayo Clinic Florida had support from a Morris K. Udall Parkinson's Disease Research Center of Excellence (NINDS P50 #NS072187), CurePSP and the Tau Consortium. The samples from the University of Pennsylvania are supported by NIA grant P01AG017586.