SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment DOI Creative Commons
Guadalupe Pereyra,

María Inés Mateo,

Pablo Miaja

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115535 - 115535

Published: April 1, 2025

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

Language: Английский

Humanized rodent models of neurodegenerative diseases and other brain disorders DOI
X.B Zhang, Jianxiang Wang, Jiewen Zhang

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 106112 - 106112

Published: March 1, 2025

Language: Английский

Citations

0
SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment DOI Creative Commons
Guadalupe Pereyra,

María Inés Mateo,

Pablo Miaja

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115535 - 115535

Published: April 1, 2025

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

Language: Английский

Citations

0