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April 12, 2025
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SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment.

Publicated to: Cell Reports. 44 (4): 115535-115535 - 2025-04-07 44(4), DOI: 10.1016/j.celrep.2025.115535

Authors: Pereyra G; Mateo MI; Miaja P; Martin-Bermejo MJ; Martinez-Baños M; Klaassen R; Gruart A; Rueda-Carrasco J; Fernández-Rodrigo A; López-Merino E; Esteve P; Esteban JA; Smit AB; Delgado-García JM; Bovolenta P

Affiliations

Center for Neurogenomics and Cognitive Research, VU University Amsterdam, 1081 Amsterdam, the Netherlands. - Author
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Campus de la Universidad Autónoma de Madrid, 28049 Madrid, Spain. - Author
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Campus de la Universidad Autónoma de Madrid, 28049 Madrid, Spain; CIBER de Enfermedades Raras (CIBERER), 28029 Madrid, Spain. - Author
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Campus de la Universidad Autónoma de Madrid, 28049 Madrid, Spain; CIBER de Enfermedades Raras (CIBERER), 28029 Madrid, Spain. Electronic address: pbovolenta@cbm.csic.es. - Author
División de Neurociencias, Universidad Pablo de Olavide, 41013 Seville, Spain. - Author
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Abstract

Impaired neuronal and synaptic function are hallmarks of early Alzheimer's disease (AD), preceding other neuropathological traits and cognitive decline. We previously showed that SFRP1, a glial-derived protein elevated in AD brains from preclinical stages, contributes to disease progression, implicating glial factors in early pathogenesis. Here, we generate and analyze transgenic mice overexpressing astrocytic SFRP1. SFRP1 accumulation causes early dendritic and synaptic defects in adult mice, followed by impaired synaptic long-term potentiation and cognitive decline, evident only when the animals age, thereby mimicking AD's structural-functional temporal distinction. This phenotype correlates with proteomic changes, including increased structural synaptic proteins like neurexin, which localizes in close proximity with SFRP1 in cultured hippocampal neurons. We conclude that excessive SFRP1 hinders synaptic protein turnover, reducing synaptic plasticity-a mechanism that may underlie the synaptopathy observed in the brains of prodromal AD patients.

Keywords

Adam10Alzheimer’s diseaseAstrocytesCp: neuroscienceDendritic spinesMicrogliaNeurexinNeurodegenerationProteomicsStructural synaptic moleculesSynaptic plasticity

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cell Reports due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 44/204, thus managing to position itself as a Q1 (Primer Cuartil), in the category Cell Biology.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-07:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 9.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 9 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 44.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).
  • The number of mentions on Wikipedia: 1 (Altmetric).
  • The number of mentions in news outlets: 5 (Altmetric).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Netherlands.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Pereyra G) and Last Author (Bovolenta P).