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 900 PSP samples for whole-genome sequencing (WGS) of neuropathologically characterized PSP. About half of the samples come from the Mayo Clinic in Jacksonville, and the others were compiled from investigators across the US and Europe. Macrogen performed HiSeq whole genome sequencing. The Genome Center for Alzheimers Disease (GCAD) process the files with their standardized pipeline.
Daniel Geschwind, MD, PhD
University of California Los Angeles
Gerard Schellenberg, PhD
University of Pennsylvania
Funding from the Tau Consortium and CurePSP.
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 CurePSP and Tau Consortium PSP WGS data:
This project was funded by the Tau Consortium, Rainwater Charitable Foundation, and CurePSP. It was also supported by NINDS grant U54NS100693 and NIA 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. Tissues were received from the Victorian Brain Bank, supported by The Florey Institute of Neuroscience and Mental Health, The Alfred and the Victorian Forensic Institute of Medicine and funded in part by Parkinson’s Victoria and MND Victoria. We are grateful to the Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona for the provision of human biological materials (or specific description, e.g. brain tissue, cerebrospinal fluid). The Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services ( contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium) and the Michael J. Fox Foundation for Parkinson's Research. Biomaterial was provided by the Study Group DESCRIBE of theClinical Research of the German Center for Neurodegenerative Diseases (DZNE).