PXD075656

PXD075656 is an original dataset announced via ProteomeXchange.

Title	Longitudinal Proteomic Profiling Defines a Two-Stage Remodeling Trajectory of Tauopathy in PS19 Mice
Description	Tauopathies, including Alzheimer’s disease (AD), are characterized by progressive synaptic dysfunction, neuroinflammation, and neuronal loss. Across neuropathological and in vivo imaging studies, tau pathology shows a consistently tight relationship with cognitive impairment and neurodegeneration, often exceeding correlations observed for amyloid plaque burden, highlighting tau as a central determinant of clinical decline[1]. However, the temporal molecular transitions that connect early synaptic vulnerability to later inflammatory amplification and neurodegeneration remain incompletely defined. Here, we performed a longitudinal, label-free data-independent acquisition (DIA) proteomic profiling of brain tissues from PS19 (P301S) tau transgenic mice at 5, 6, and 7 months of age, together with 5-month noncarrier littermate controls. Comparative analysis at 5 months confirmed early tau-associated alterations involving synaptic organization, cytoskeletal regulation, and stress-responsive signaling pathways, consistent with prior reports that synapse loss and microglial activation can precede mature tau tangles in P301S/PS19-related models[2-5]. Furthermore, longitudinal profiling identified 776 significantly altered proteins (FDR < 0.05) that segregated into four distinct temporal expression patterns. These trajectories delineate a two-stage disease course, with an initial adaptive phase (5–6 months) marked by synaptic down-tuning and metabolic stress responses, followed by a transition toward an inflammatory and degenerative state (6–7 months). Notably, 6 months emerged as a molecular transition point characterized by coordinated activation of stress-associated signaling pathways. This transition timing is consistent with PS19/P301S literature indicating prominent neurofibrillary tangles (NFT) pathology around ~6 months with subsequent neurodegenerative escalation[6].
HostingRepository	iProX
AnnounceDate	2026-03-15
AnnouncementXML	Submission_2026-03-16_00:01:18.349.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shuaixin Gao
SpeciesList	scientific name: Mus sp.; NCBI TaxID: 10095;
ModificationList	acetylated residue
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-16 00:00:47	ID requested
⏵ 1	2026-03-16 00:01:18	announced

Dataset with its publication pending

submitter keyword: Tauopathy, Alzheimer’s disease, PS19, P301S, DIA proteomics, Longitudinal profiling

Synaptic dysfunction, Neuroinflammation

Complement, Excitotoxicity

Jiangjiang Zhu
contact affiliation	The Ohio State University
contact email	zhu.2484@osu.edu
lab head
Shuaixin Gao
contact affiliation	The Ohio State University
contact email	nzhangwe@outlook.com
dataset submitter

iProX dataset URI