Fibrinogen-tau Aggregates Exacerbate Tau Pathology and Memory Deficits in Alzheimer's Disease Model Mice.
10.1007/s12264-025-01366-8
- Author:
Tingting WEN
1
;
Lanxia MENG
1
;
Han LIU
1
;
Qian ZHANG
1
;
Lijun DAI
1
;
Liqin HUANG
1
;
Liang DAN
1
;
Kedong ZHU
1
;
Jiaying LUO
1
;
Zhaohui ZHANG
2
,
3
Author Information
1. Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
2. Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. zhzhqing1990@
3. com.
- Publication Type:Journal Article
- Keywords:
Alzheimer’s disease;
Cross-seeding;
Fibrinogen;
Tauopathy
- MeSH:
Animals;
tau Proteins/metabolism*;
Alzheimer Disease/metabolism*;
Fibrinogen/metabolism*;
Mice, Transgenic;
Mice;
Disease Models, Animal;
Memory Disorders/metabolism*;
Male;
Mice, Inbred C57BL;
Brain/metabolism*;
Hippocampus/metabolism*;
Protein Aggregation, Pathological/metabolism*;
Apoptosis;
Phosphorylation
- From:
Neuroscience Bulletin
2025;41(7):1246-1260
- CountryChina
- Language:English
-
Abstract:
Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
