PXD056771-1

PXD056771 is an original dataset announced via ProteomeXchange.

Title	Astrocytic EphA4 signaling is important for the elimination of excitatory synapses in Alzheimer’s disease
Description	Cell surface receptors, including erythropoietin-producing hepatocellular A4 (EphA4), are important in regulating hippocampal synapse loss, which is the key driver of memory decline in Alzheimer’s disease (AD). However, the cellular-specific roles and mechanisms of EphA4 are unclear. Here, we show that EphA4 expression is elevated in hippocampal CA1 astrocytes in AD conditions. Specific knockout of astrocytic EphA4 ameliorates excitatory synapse loss in the hippocampus in AD transgenic mouse models. Single-nucleus RNA sequencing analysis revealed that EphA4 inhibition specifically decreases a reactive astrocyte subpopulation with enriched complement signaling, which are characteristics associated with synapse elimination by astrocytes in AD. Importantly, astrocytic EphA4 knockout in an AD transgenic mouse model decreases complement tagging on excitatory synapses and excitatory synapses within astrocytes. These findings suggest an important role of EphA4 in the astrocyte-mediated elimination of excitatory synapses in AD and highlight the crucial role of astrocytes in hippocampal synapse maintenance in AD.
HostingRepository	PRIDE
AnnounceDate	2025-01-06
AnnouncementXML	Submission_2025-01-06_07:40:43.571.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xin YANG
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-13 21:23:06	ID requested
⏵ 1	2025-01-06 07:40:44	announced

10.1073/PNAS.2420324122;

submitter keyword: LC-MSMS,Mouse, Brain

Nancy Ip
contact affiliation	Room 6313, Academic building, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon
contact email	iplabgenetics@gmail.com
lab head
Xin YANG
contact affiliation	Hong Kong University of Science and Technology
contact email	xyangaq@connect.ust.hk
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/2025/01/PXD056771

PRIDE project URI

• PRIDE
  1. PXD056771
     1. Label: PRIDE project
     2. Name: Astrocytic EphA4 signaling is important for the elimination of excitatory synapses in Alzheimer’s disease