PXD067593

PXD067593 is an original dataset announced via ProteomeXchange.

Title	Tau Profiling of Brain Extracellular Vesicles Reveals PHF6 Peptide as Core for Pathological Tau Seeding in Alzheimer's Disease
Description	EVs are bilipid spheres known for their role in cellular communication through transport of proteins, lipids, RNA and more. In the brain, EVs are directly released in the interstitial fluid surrounding neural cells and hence entitled brain-derived EVs (BD-EVs). Human BD-EVs of AD patients contain seed-competent tau. Further, we demonstrated a different tau seeding capacity of AD, PSP and PiD patients derived EVs. This reflects a heterogenous contribution of BD-EVs to tau seeding among tauopathies, with AD BD-EVs showing the highest seeding capacity. Here, we aim to identify and compare the tau proteoforms found within EVs of tauopathies to assess if this tau content lays at the base of the heterogeneity observed for EVs seeding among tauopathies. A tau immunoprecipitation followed by mass spectrometry analysis (tau IP-MS), performed on BD-EVs from non-demented controls or patients affected with different tauopathies, revealed detection of 22 tryptic tau peptides with two MTBR tryptic peptides enriched only in AD BD-EVs. Among them, the well-known pro-aggregative hexapeptide PHF6 (VQIVYK) was found. Importantly, we demonstrated that PHF6-containing tau proteins are strongly implied in the seeding capacity of AD BD-EVs. From this, we conclude that the PHF6 is a driver for the higher EVs-mediated tau propagation in AD patients, revealing an interesting therapeutic target to prevent tau pathology spreading.
HostingRepository	PanoramaPublic
AnnounceDate	2026-09-06
AnnouncementXML	Submission_2026-09-06_13:21:11.379.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Laura Fichter
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	GG; Phospho; Oxidation; Label:15N(1); Label:15N(2); Label:15N(3); Label:15N(4)
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-21 22:44:48	ID requested
⏵ 1	2026-09-06 13:21:12	announced

Oosterlynck M, Fichter L, Leroux E, Eddarkaoui S, Bouillet T, Lefebvre C, Nguyen M, Maurage CA, Accart B, Dupr, é E, Landrieu I, Danis C, Lehmann S, Vialaret J, Bu, é, e L, Hirtz C, Colin M, Tau profiling of brain extracellular vesicles reveals PHF6 peptide as core for pathological tau seeding in Alzheimer's disease. J Biomed Sci, 33(1):(2026) [pubmed]

submitter keyword: Tauopathies, Alzheimer’s disease, Extracellular Vesicles, Seeding, Tau proteoforms, PHF6 peptide

Jerome VIALARET
contact affiliation	PPC-LBPC, Université de Montpellier, INM INSERM, IRMB CHU de Montpellier, Montpellier, France
contact email	jerome_vialaret@yahoo.fr
lab head
Laura Fichter
contact affiliation	PPC-LBPC, Université de Montpellier, INM INSERM, IRMB CHU de Montpellier, Montpellier, France
contact email	l-fichter@chu-montpellier.fr
dataset submitter

Panorama Public dataset URI