PXD032192

PXD032192 is an original dataset announced via ProteomeXchange.

Title	Proteopathic tau seeds contain key similarities to mature paired helical filaments in Alzheimer disease
Description	Proteopathic seeds are soluble species of aggregation prone molecules such as tau, that are competent to instruct endogenous proteins to undergo templated misfolding. Yet the idea of proteopathic seeds for tau is largely abstract, and the relationship of the seeds to the final fibrils that define the diseases has not been determined. We utilized mass spectrometry (MS), and in vitro bioassays to characterize the soluble tau species, derived from human Alzheimer brain, that are capable of inducing tau seeding in bioreporter cells and in vivo. Multiple post translational modifications (PTM) were identified by MS, including phosphorylations, acetylations, and ubiquitinations. While the patterns are quite similar to that of post translational modifications on insoluble paired helical filament preparations, the presence of fewer overall post translational modifications, and some unique modifications, distinguish soluble seed competent tau from filamentous tau in Alzheimer disease. Surprisingly, the presence of ubiquitin modifications on the soluble seed competent species correlates positively with bioactivity, and the stoichiometry of ubiquitin occupancy and other PTMs¬ correlate with the aggressiveness of clinical disease measured by age of onset and rapidity of progression. These results define the bioactive, seed competent tau species as being closely related to, but distinct from, mature paired helical filaments, and provide insight into the molecular features of tau PTMs that ultimately generate the bioactive conformation of tau present in Alzheimer disease (AD).
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:38:57.521.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	ubiquitinylated lysine; phosphorylated residue; acetylated residue
Instrument	timsTOF Pro; QTRAP 5500

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-11 06:58:10	ID requested
⏵ 1	2025-05-06 09:38:58	announced

10.1093/brain/awad378;

Kumar M, Quittot N, Dujardin S, Schlaffner CN, Viode A, Wiedmer A, Beerepoot P, Chun JE, Glynn C, Fernandes AR, Donahue C, Steen JA, Hyman BT, Alzheimer proteopathic tau seeds are biochemically a forme fruste of mature paired helical filaments. Brain, 147(2):637-648(2024) [pubmed]

submitter keyword: Alzheimer's disease

Post-translational modification

SRM

LFQ

Human Tau

Protein aggregation

Proteopathy

Clinical progression

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

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PRIDE project URI

• PRIDE
  1. PXD032192
     1. Label: PRIDE project
     2. Name: Proteopathic tau seeds contain key similarities to mature paired helical filaments in Alzheimer disease