PXD066225-1

PXD066225 is an original dataset announced via ProteomeXchange.

Title	IgLON5 autoimmune antibodies activate Tau via neuronal hyperactivity
Description	Anti-IgLON5 disease is an autoimmunity/neurodegeneration overlap disorder, in which autoantibodies (AABs) against the neuronal cell surface protein IgLON5 lead to profound brain dysfunction. Whether neuronal Tau protein pathology and neurodegeneration found in the patient’s brains are directly related to anti-IgLON5 AABs remains unclear. We find that patient-derived anti-IgLON5 AABs induce the clustering of cell surface IgLON5 with other proteins, leading to acute neuronal hyperactivity that triggers pro-pathological Tau missorting and phosphorylation, typically observed early in Tau-related neurodegenerative diseases. In wildtype mice, anti-IgLON5 AABs induce hippocampal Tau phosphorylation and neuroinflammatory responses. These findings provide first direct evidence that anti-IgLON5 AABs are causally linked to Tau pathology in anti-IgLON5 disease patients, thereby providing important new insights into the disease mechanisms, and highlight the role of neuronal hyperactivity as a disease-overarching driver of Tau pathology.
HostingRepository	PRIDE
AnnounceDate	2026-05-22
AnnouncementXML	Submission_2026-05-21_21:50:36.484.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karsten Nalbach
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-16 14:07:54	ID requested
⏵ 1	2026-05-21 21:50:36	announced

10.1126/SCIADV.AEC2042;

10.1126/sciadv.aec2042;

submitter keyword: None

Stefan Lichtenthaler
contact affiliation	DZNE Munich / TU Munich
contact email	stefan.lichtenthaler@dzne.de
lab head
Karsten Nalbach
contact affiliation	DZNE Munich / TU Munich
contact email	karsten.nalbach@dzne.de
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/2026/05/PXD066225

PRIDE project URI

• PRIDE
  1. PXD066225
     1. Label: PRIDE project
     2. Name: IgLON5 autoimmune antibodies activate Tau via neuronal hyperactivity