.png){kind=icon}
.png){kind=icon}
Return
Preclinical assessment of intravenous human ficolin-2 administration for Alzheimer's disease
.png){kind=icon}
OA
AI
X
Y
Q
H
X
B
L
T
L
P
Q
Q
E
Q
H
X
Q
Q
Y
Y
DOI：10.1016/j.gendis.2026.102391.png)
.png){kind=icon}
.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Circulatory proteins secreted by peripheral organs exert regulatory effects on the brain. This preclinical study aimed to identify circulatory proteins for treating Alzheimer's disease (AD). Proteomics was performed to determine the AD-related serum proteins. The changes in the serum levels of key proteins were further validated between healthy and AD participants using ELISA. Mendelian randomization (MR) analysis was used to identify circulatory proteins for treating AD. We assessed their origins based on transcription and protein profiles from human organs. AD mice were treated with recombinant human ficolin-2 (FCN2) protein or specifically expressed human FCN2 in the liver. Hippocampal neuropathological parameters and alterations of cellular gene expression in response to the therapy were evaluated via single-nucleus RNA-sequencing (snRNA-seq). FCN2, LCT, TXNL4B, and SLAMF7 had protective effects on AD. FCN2 was reduced in the serum of AD patients, which was positively correlated with poor cognitive performance. Recombinant human FCN2 ameliorated cognitive decline, pathology, and synaptic impairment in AD mice. Liver replenishment of human FCN2 improved the cognitive function of AD mice and attenuated AD pathology. Hippocampal snRNA-seq revealed that human FCN2 suppresses AD-related pathological processes in AD mice, while it enhances pathways involved in Aβ clearance, learning, memory, and synaptic homeostasis, promoting interactions between hippocampal cells via synapse-related ligand‒receptor signaling. The imbalance of peripheral proteins negatively impacts AD pathogenesis and cognition, identifying a liver-to-brain axis by which blood factors can regulate AD risk. Supplementing human FCN2 is sufficient to rescue AD pathology and cognitive impairment in AD mice.
Keywords:
Alzheimer's disease
circulatory protein
FCN2
Synaptic homeostasis
Mendelian randomization
AI Summary
Key information extracted from the uploaded paper, including a brief overview, abstract, background, key highlights, visual analysis, and future outlook.
Journal
G
IF:
9.4
Papers:
304
Citations:
0
Organization
No organization information available
Cited Papers