Fibrinogen-tau Aggregates Exacerbate Tau Pathology and Memory Deficits in Alzheimer’s Disease Model Mice
Tingting Wen1 · Lanxia Meng1 · Han Liu1 · Qian Zhang1 · Lijun Dai1 · Liqin Huang1 · Liang Dan1 · Kedong Zhu1 · Jiaying Luo1 · Zhaohui Zhang11 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China
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.
Keywords
Fibrinogen; Tauopathy; Cross-seeding; Alzheimer’s disease
