PXD069785

PXD069785 is an original dataset announced via ProteomeXchange.

Title	High-fat diet and a high amyloid load interact to induce PKC-α dependent synaptic insulin resistance
Description	Synaptic insulin resistance has been proposed as a mechanistic link between high-fat diet exposure, elevated amyloid burden, and vulnerability to Alzheimer’s disease. To investigate molecular changes associated with this state at the synapse, we performed integrated global proteomic and phosphoproteomic profiling of hippocampal synaptosomes isolated from wild-type mice and heterozygous TBA2.1 mice (high amyloid load without overt neurodegeneration) maintained either on a regular or high-fat diet. Proteins and phosphosites were quantified by data-independent acquisition (DIA), identifying >5,400 proteins across experimental conditions. While the baseline synaptic proteome remained largely stable, the combination of amyloid load and high-fat diet was associated with coordinated remodeling of lipid metabolism pathways, with signatures pointing to mitochondrial and peroxisomal fatty acid catabolism. Phosphoproteomics revealed activation of lipid- and stress-responsive kinase pathways, including PKC-α, and increased inhibitory phosphorylation of IRS1/2. Complementary in vitro assays confirmed that pharmacological inhibition of PKC-α prevented the emergence of synaptic insulin resistance in primary neurons. These datasets provide a resource for studying diet- and amyloid-dependent signaling alterations at the synapse in the context of Alzheimer’s-relevant disease drivers.
HostingRepository	PRIDE
AnnounceDate	2026-04-13
AnnouncementXML	Submission_2026-04-12_17:10:38.707.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexander Wenger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-22 11:15:54	ID requested
⏵ 1	2026-04-12 17:10:39	announced

Wenger A, Li T, Nguyen C, Celik A, Cuboni E, Dityatev A, Karpova A, Kreutz MR, Ahrends R, Dependent Synaptic Insulin Resistance. Mol Cell Proteomics, 25(4):101537(2026) [pubmed]

10.1016/j.mcpro.2026.101537;

submitter keyword: None

Robert Ahrends
contact affiliation	University of Vienna, Faculty of Chemistry, Department of Analytical Chemistry
contact email	robert.ahrends@univie.ac.at
lab head
Alexander Wenger
contact affiliation	University of Vienna/ Dep. of Chemistry/ Fac. of Analytical Chemistry
contact email	alexander.wenger@univie.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069785
     1. Label: PRIDE project
     2. Name: High-fat diet and a high amyloid load interact to induce PKC-α dependent synaptic insulin resistance