PXD060276-1

PXD060276 is an original dataset announced via ProteomeXchange.

Title	SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment
Description	Impaired neuronal and synaptic function are hallmarks of early stages Alzheimer's disease (AD) and are linked to cognitive decline, preceding other neuropathological traits. We have previously shown that SFRP1, a glial-derived protein elevated in the brains of AD patients from preclinical stages, contributes to AD progression, suggesting that glial factors may be important for early pathogenesis. Here, we have analyzed the hippocampus of newly generated transgenic mice overexpressing SFRP1 in astrocytes. We show that SFRP1 accumulation causes early dendritic and synaptic structural defects in adult mice. These changes are followed by poor synaptic long-term potentiation and cognitive impairment, evident only when the animals age, thereby mimicking the structural-functional temporal distinction observed in AD patients. These phenotypic traits are associated with an array of proteomic changes, including increased content of structural synaptic proteins, such as neurexin, which localizes in close proximity to SFRP1 along the processes of cultured hippocampal neurons. We conclude that excessive SFRP1 prevents the turnover of structural synaptic molecules, thereby reducing synaptic plasticity —a mechanism that may mirror the synaptopathy observed in the brains of prodromal AD patients.
HostingRepository	PRIDE
AnnounceDate	2026-01-19
AnnouncementXML	Submission_2026-01-19_07:30:25.530.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Remco Klaassen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-28 05:03:33	ID requested
⏵ 1	2026-01-19 07:30:26	announced

10.1016/J.CELREP.2025.115535;

submitter keyword: TimsTOF Pro 2,Mouse

Paola Bovolenta
contact affiliation	Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Campus de la Universidad Autónoma de Madrid, Spain
contact email	pbovolenta@cbm.csic.es
lab head
Remco Klaassen
contact affiliation	Department of Molecular and Cellular Neurobiology. Vrije Universiteit Amsterdam.
contact email	r.v.klaassen@vu.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060276
     1. Label: PRIDE project
     2. Name: SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment