PXD077817-1

PXD077817 is an original dataset announced via ProteomeXchange.

Title	TMT-based total protein and phosphopeptide quantification of mouse brain with human Tau insert
Description	The gut microbiome modulates metabolic and neurovascular processes implicated in Alzheimer’s disease and related dementias (ADRD), but the underlying mechanisms remain unclear. Here, we identify the bacterial metabolite imidazole propionate (ImP) as a modifier of ADRD pathology. In a cohort of 1,196 cognitively unimpaired adults, higher plasma ImP levels were associated with lower preclinical cognitive scores and biomarkers of ADRD, both cross-sectionally and longitudinally. Fecal metagenomic analysis linked putative ImP producers to ADRD phenotypes. Genome-wide integrative analysis revealed a locus on chromosome 12 associated with both plasma ImP levels and AD risk in humans, supporting a host genetic contribution to ImP regulation and a causal role of this metabolite in AD. In mice, chronic ImP administration exacerbated AD-like pathology. Mechanistically, ImP impaired brain endothelial barrier and promoted tau hyperphosphorylation in primary neurons, an effect blocked by glycogen synthase kinase-3β inhibition. Together, our study links ImP to hallmarks of neurodegeneration and suggest that targeting ImP may represent a potential strategy to modify ADRD risk.
HostingRepository	PRIDE
AnnounceDate	2026-08-18
AnnouncementXML	Submission_2026-08-18_07:08:14.103.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD077817
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Greg Sabat
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; TMT6plex reporter fragment; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-29 14:43:59	ID requested
⏵ 1	2026-08-18 07:08:14	announced

10.1038/s41467-026-74744-z;

10.6019/PXD077817;

Vemuganti V, Kang JW, Zhang Q, McGregor ER, Hilser JR, Aquino-Martinez R, Harding S, Harpt JL, Beck KR, Bussan H, Kuehn JF, Deming Y, Studer R, Johnson SC, Asthana S, Zetterberg H, Blennow K, Engelman CD, Allayee H, Anderson RM, Ulland TK, B, ä, ckhed F, Bendlin BB, Rey FE, Gut bacterial metabolite imidazole propionate potentiates Alzheimer's disease pathology. Nat Commun, 17(1):(2026) [pubmed]

submitter keyword: TMTpro, amyloid, phosphoproteomics,Alzheimer

Dr. Federico Rey
contact affiliation	Bacteriology Department, University of Wisconsin-Madison
contact email	ferey@wisc.edu
lab head
Greg Sabat
contact affiliation	University of Wisconsin
contact email	gsabat@wisc.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/2026/08/PXD077817

PRIDE project URI

• PRIDE
  1. PXD077817
     1. Label: PRIDE project
     2. Name: TMT-based total protein and phosphopeptide quantification of mouse brain with human Tau insert