PXD020717-1

PXD020717 is an original dataset announced via ProteomeXchange.

Title	Quantitative PTM Maps of Human Pathologic Tau Identify Patient Heterogeneity and Define Critical Steps in Alzheimer’s Disease Progression - frontal gyrus (sarkosyl soluble)
Description	To elucidate the role of Tau isoforms and PTM stoichiometry in Alzheimer’s disease (AD), we generated a high resolution quantitative proteomic map of 88 PTMs on multiple isoforms of Tau isolated from the post-mortem human tissue from 49 AD and 42 control subjects. While Tau PTM maps reveal heterogeneity across subjects, a subset of PTMs display high occupancy and patient frequency for AD suggesting importance in disease. Unsupervised analyses indicate that PTMs occur in an ordered manner leading to Tau aggregation. The processive addition and minimal set of PTMs associated with seeding activity was further defined by the analysis of size fractionated Tau. To summarize, critical features within the Tau protein for disease intervention at different stages of disease are identified, including enrichment of 0N and 4R isoforms, underrepresentation of the C-terminal, an increase in negative charge in the PRR and a decrease in positive charge in the MBD.
HostingRepository	PRIDE
AnnounceDate	2020-12-04
AnnouncementXML	Submission_2020-12-04_00:10:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christoph Schlaffner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; phosphorylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-03 22:23:56	ID requested
⏵ 1	2020-12-04 00:10:07	announced

Wesseling H, Mair W, Kumar M, Schlaffner CN, Tang S, Beerepoot P, Fatou B, Guise AJ, Cheng L, Takeda S, Muntel J, Rotunno MS, Dujardin S, Davies P, Kosik KS, Miller BL, Berretta S, Hedreen JC, Grinberg LT, Seeley WW, Hyman BT, Steen H, Steen JA, Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer's Disease. Cell, 183(6):1699-1713.e13(2020) [pubmed]

submitter keyword: Alzheimer's disease

Post-translational modification

clinical progression

SRM

LFQ

Human Tau

Protein aggregation

Proteopathy

Judith A. Steen
contact affiliation	Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
contact email	judith.steen@childrens.harvard.edu
lab head
Christoph Schlaffner
contact affiliation	Boston Children's Hospital; Harvard Medical School
contact email	christoph.schlaffner@childrens.harvard.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/12/PXD020717

PRIDE project URI

• PRIDE
  1. PXD020717
     1. Label: PRIDE project
     2. Name: Quantitative PTM Maps of Human Pathologic Tau Identify Patient Heterogeneity and Define Critical Steps in Alzheimer’s Disease Progression - frontal gyrus (sarkosyl soluble)