PXD045861-1

PXD045861 is an original dataset announced via ProteomeXchange.

Title	Myelin-axon interface disruption uncovered by subcellular proteomics and imaging of Alzheimer’s human brain
Description	Myelin ensheathment enables efficient axonal electrical conduction, metabolic support, and regulates neuronal plasticity. Myelin and axon disruptions are involved in Alzheimer’s disease (AD), however, the precise mechanisms of how myelin and axons are decoupled remain poorly understood. Using novel subcellular proximity labeling proteomics, we characterizeduncovered the myelin-axon interface proteomeics in AD human postmortem brains and unaffected controls. We identified AD-dysregulated ligand-receptors and downstream signaling, such as amyloid processing and axonogenesis, that are involved in myelin-axon interaction. Using high resolution imaging approaches, we revealed structural abnormality of paranodes, and corroborated proteomic evidence showing intrusion of amyloid fibers at the internodal peri-axonal space and paranodal channels. We also revealed aberrant myelin and paranodes are associated with axonal spheroids around amyloid plaques. Together, this study reveals myelin-axon interface as a vulnerable site in AD, and provides novel techniques and resources to delineate the complex molecular and cellular interaction between myelin and axons in AD and beyond.
HostingRepository	PRIDE
AnnounceDate	2025-06-27
AnnouncementXML	Submission_2025-06-27_05:34:19.205.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; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-02 09:00:58	ID requested
⏵ 1	2025-06-27 05:34:20	announced

10.1038/s41593-025-01973-8;

Cai Y, Pinheiro-de-Sousa I, Slobodyanyuk M, Chen F, Huynh T, Kanyo J, Tang P, Fuentes LA, Braker A, Welch R, Huttner A, Tong L, Yuan P, Lam TT, Petsalaki E, Reimand J, Nairn AC, Grutzendler J, Myelin-axon interface vulnerability in Alzheimer's disease revealed by subcellular proteomics and imaging of human and mouse brain. Nat Neurosci, ():(2025) [pubmed]

submitter keyword: LC-MS-MS, subcellular proteomics, Alzheimer's disease, proximity labeling,Human brain, myelin-axon interface

Jaime Grutzendler
contact affiliation	Yale University, Department of Neurology and Neuroscience
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/2025/06/PXD045861

PRIDE project URI

• PRIDE
  1. PXD045861
     1. Label: PRIDE project
     2. Name: Myelin-axon interface disruption uncovered by subcellular proteomics and imaging of Alzheimer’s human brain