PXD060761

PXD060761 is an original dataset announced via ProteomeXchange.

Title	Targeting CD38 immunometabolic checkpoint improves metabolic fitness and cognition in a mouse model of Alzheimer’s disease
Description	Protective immunity, essential for brain maintenance and repair, may be compromised in Alzheimer’s disease (AD). Here, using high-dimensional single-cell mass cytometry, we find a unique immunometabolic signature in circulating CD4+ T cells preceding symptom onset in individuals with familial AD, featured by the elevation of CD38 expression. Using female 5xFAD mice, a mouse model of AD, we show that treatment with an antibody directed to CD38 leads to restored metabolic fitness, improved cognitive performance, and attenuated local neuroinflammation. Comprehensive profiling across distinct immunological niches in 5xFAD mice, reveals a high level of disease-associated CD4+ T cells that produce IL-17A in the dural meninges, previously linked to cognitive decline. Targeting CD38 leads to abrogation of meningeal TH17 immunity and cortical IL-1beta, breaking the negative feedback loop between these two compartments. Taken together, the present findings suggest CD38 as an immunometabolic checkpoint that could be adopted as a pre-clinical biomarker for early diagnosis of AD and might also be therapeutically targeted alone or in combination with other immunotherapies for disease modification.
HostingRepository	PRIDE
AnnounceDate	2025-03-08
AnnouncementXML	Submission_2025-03-08_00:45:36.864.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alon Savidor
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; deaminated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-13 01:18:53	ID requested
⏵ 1	2025-03-08 00:45:37	announced

Dataset with its publication pending

submitter keyword: LC-MSMS, Mus musculus, CD38,CSF, Alzheimer's disease

Prof. Michal Schwartz
contact affiliation	Department of Brain Sciences Faculty of Biology Weizmann Institute of Science 234 Herzl Street Rehovot 7610001 Israel
contact email	michal.schwartz@weizmann.ac.il
lab head
Alon Savidor
contact affiliation	The Weizmann Institute of Science
contact email	alon.savidor@weizmann.ac.il
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/2025/03/PXD060761

PRIDE project URI

• PRIDE
  1. PXD060761
     1. Label: PRIDE project
     2. Name: Targeting CD38 immunometabolic checkpoint improves metabolic fitness and cognition in a mouse model of Alzheimer’s disease