Dataset Information

SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Remco Klaassen

LAB HEAD: Paola Bovolenta

PROVIDER: PXD060276 | Pride | 2026-01-19

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20220812_rklaas_CBMSO-SFRP1_DIA-NN-search.zip	Other
	20220812_rklaas_CBMSO-SFRP1_DIA_G1-S1_S1-A1_1_4902.d.zip	Other
	20220812_rklaas_CBMSO-SFRP1_DIA_G1-S2_S1-A2_1_4903.d.zip	Other
	20220812_rklaas_CBMSO-SFRP1_DIA_G1-S3_S1-A3_1_4904.d.zip	Other
	20220812_rklaas_CBMSO-SFRP1_DIA_G1-S4_S1-A4_1_4905.d.zip	Other

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SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment

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