PXD048097

PXD048097 is an original dataset announced via ProteomeXchange.

Title	Lamp1 proximity labeling proteomics in 5XFAD mice
Description	Plaque-associated axonal spheroids (PAAS) are frequently observed around amyloid deposits in Alzheimer's disease (AD) and are known to impair axonal electrical conduction, disrupt neural circuits, and correlate with AD severity. Despite their significance, the mechanisms underlying PAAS formation remain largely unknown. To explore this, we developed a proximity labeling proteomics approach to identify the PAAS proteome in human postmortem brains and mice. Additionally, we established a human iPSC-derived AD model allowing structural, optical electrophysiology, and mechanistic investigation of PAAS pathology. This approach revealed the molecular architecture of PAAS and identified dysregulated biological processes, including protein turnover, cytoskeleton dynamics, and lipid transport. Activated PI3K/AKT/mTOR pathway, which regulates these processes, was expressed in PAAS and strongly correlated with AD severity in humans. Inhibition of mTOR in human iPSC-derived neurons and in mice led to a marked reduction in PAAS. Our study provides a multidisciplinary toolkit for investigating axonal pathology and identifying novel targets for neurodegeneration.
HostingRepository	PRIDE
AnnounceDate	2025-02-20
AnnouncementXML	Submission_2025-02-20_12:15:17.438.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yifei Cai
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-23 11:58:46	ID requested
⏵ 1	2025-02-20 12:15:17	announced

10.1038/S43587-025-00823-3;

submitter keyword: subcellular proteomics,Lamp1, proximity labeling, Alzheimer's disease, 5XFAD mouse

Jaime Grutzendler
contact affiliation	Department of Neurology and Neuroscience, Yale University
contact email	jaime.grutzendler@yale.edu
lab head
Yifei Cai
contact affiliation	Yale University
contact email	yifeicaichina@gmail.com
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/2025/02/PXD048097

PRIDE project URI

• PRIDE
  1. PXD048097
     1. Label: PRIDE project
     2. Name: Lamp1 proximity labeling proteomics in 5XFAD mice