PXD057993

PXD057993 is an original dataset announced via ProteomeXchange.

Title	ABPP using chemical proteomics in Alzheimer's Disease and Resilience
Description	pulldown on enzymes targeted by serine hydrolase probes tetrahydrolipstatin-biotin and fluorophosphonate biotin probe in lysates from the frontal cortex of 36 patients (12 conrol, 12 Alzheimer's, 12 Resilient). below is the abstract: Alzheimer’s Disease (AD) is the most common form of dementia. While it has become clear that alterations in lipid metabolism are associated with AD, it is not well understood how they contribute to both cognitive decline and the pathophysiology of AD. To better understand these changes, we performed lipidomics and activity-based proteomic profiling (ABPP) in the frontal cortex of a cohort of control, AD and resilient donors, the latter referring to individuals with AD pathology without declined cognition. We demonstrate that most changes in the lipidome are related to AD pathology. The class of lipids most strongly changed was ω6-derived oxylipins, which reflect a neuroinflammatory response. This lipid class was particularly increased in the AD patients compared to controls, while it showed a similar but non-significant trend in resilient donors. In contrast, both triacylglycerides (TAGs) and lipid droplets were more abundant in the AD donors compared to the resilient donors, but not to the control donors, indicating alterations in neutral lipids in resilient donors. Enzyme activities profiled by ABPP showed a similar direction in the AD and resilient donors, including decreased activity of ABHD6, a lipase involved in mono-acyl glycerol metabolism. Finally, using multi-omics factor analysis, we show that increased oxylipins, loss of inhibitory cells and reduced synaptic plasticity are associated with Aβ plaque load. This response was present in both the AD and resilient donors. Taken together, our multi-omics data show a response associated with Aβ load shared among AD and resilient donors and, for the first time, reduced lipid droplets in resilient donors.
HostingRepository	PRIDE
AnnounceDate	2026-02-09
AnnouncementXML	Submission_2026-02-08_16:55:46.227.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Daan Van der Vliet
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-18 08:22:27	ID requested
⏵ 1	2026-02-08 16:55:47	announced

van der Vliet D, de Vries LE, Di X, Wever D, de Jong B, van der Meij MTC, van der Peet M, Harms AC, Hankemeier T, Swaab DF, Huitinga I, Verhaagen J, van der Stelt M, Reduced triacylglycerols and lipid droplets are associated with resilience to Alzheimer's disease. Alzheimers Dement, 22(2):e71083(2026) [pubmed]

10.1002/alz.71083;

submitter keyword: ABPP,Alzheimer's disease, serine hydrolases

Prof. dr. Mario van der Stelt
contact affiliation	Department of Molecular Physiology, Leiden University & Oncode Institute, Leiden 2333 CC, Netherlands
contact email	m.van.der.stelt@chem.leidenuniv.nl
lab head
Daan Van der Vliet
contact affiliation	Leiden University
contact email	d.van.der.vliet@lic.leidenuniv.nl
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/2026/02/PXD057993

PRIDE project URI

• PRIDE
  1. PXD057993
     1. Label: PRIDE project
     2. Name: ABPP using chemical proteomics in Alzheimer's Disease and Resilience