PXD061278-1

PXD061278 is an original dataset announced via ProteomeXchange.

Title	The Proteoform Landscape of Tau from the Human Brain
Description	Tau is a microtubule-associated protein (MAP) and critical for maintaining the cytoskeleton of neurons. Tau and its post-translational modifications (PTMs) have been studied for decades, yet the exact composition of intact tau and its truncation products present in the human brain have evaded study at the proteoform level. Here, our project shows tau proteoform profiling and exact characterization is possible using immunoprecipitation (IP) and the new approach of individual ion mass spectrometry (I2MS). We provide a first glimpse of the tau proteoform landscape present in the CHAPS-soluble extracts from the temporal cortex of a control subject and a donor with Alzheimer’s Disease (AD). Profiling and identification of four isoforms (0N3R, 1N3R, 0N4R, and 1N4R), truncated products (e.g., 72-172 derived from the 0N3R/0N4R isoforms), and intact tau proteoforms harboring PTMs including phosphorylation, methylation, and acetylation. The specific tau proteoform identification typically employs proton transfer charge reduction (PTCR) and electron transfer dissociation (ETD) with spectral readout by individual ion tandem mass spectrometry (I2MS2). A precise understanding of the tau proteoform landscape over the course of neurodegeneration is critical to understand AD pathology vs. related dementias. The assay approach reported here, termed ‘TauFormA’, will advance AD research, and gives a sense of what is technologically possible for new biomarker discovery and to assist the development of therapeutics using the most exact kind of compositional information on tau.
HostingRepository	PRIDE
AnnounceDate	2025-10-15
AnnouncementXML	Submission_2025-10-15_09:39:24.165.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dr. Indira Pla Parada
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	methylated residue; phosphorylated residue; acetylated residue
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-27 10:40:03	ID requested
⏵ 1	2025-10-15 09:39:24	announced

10.1021/ACS.JPROTEOME.5C00139;

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP)

submitter keyword: Tau proteoforms, Alzheimer's disease, immunoprecipitation, top-down tandem mass spectrometry, individual ion mass spectrometry

Neil Kelleher
contact affiliation	Northwestern University
contact email	n-kelleher@northwestern.edu
lab head
Dr. Indira Pla Parada
contact affiliation	Northwestern University
contact email	indira.plaparada@northwestern.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/2025/10/PXD061278

PRIDE project URI

• PRIDE
  1. PXD061278
     1. Label: PRIDE project
     2. Name: The Proteoform Landscape of Tau from the Human Brain