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.
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

Objective To investigate the change of serum osteoprotegerin level and relationships between serum osteoprotegerin level and coronary heart disease (CHD) in patients with type2 diabetes mellitus (DM) complicated with CHD.Methods One hundred and eight patients with type 2 DM complicated with CHD were selected as DM with CHD group,including 68 cases with acute coronary syndrome and 40 cases with stable angina pectoris.In addition,60 type 2 DM patients without CHD (DM without CHD group) and 40 healthy people (control group) were selected.Serum osteoprotegerin level was measured by enzyme linked immunosorbent assay.Results The serum osteoprotegerin level in DM with CHD group was significantly higher than that in DM without CHD group and control group [(4.12 ± 0.71)ng/L vs.(2.69 ± 0.52) and (2.14 ± 0.37) ng/L],and there were statistical differences (P＜ 0.05 or ＜ 0.01).In DM with CHD group,the serum osteoprotegerin level in acute coronary syndrome was significantly higher than that in stable angina pectoris [(4.56 ±0.92) ng/L vs.(3.61 ±0.76) ng/L],and there was statistical difference (P ＜ 0.05).The serum osteoprotegerin level in patients with Gensini score ＞ 40 scores (41 cases)was significantly higher than that in patients with Gensini score 20-40 scores (53 cases) and patients with Gensini score ＜ 20 scores (14 cases) [(4.92 ± 0.89) ng/L vs.(4.08 ± 0.75) and (3.39 ± 0.85) ng/L],and there were statistical differences (P ＜ 0.01 or ＜ 0.05).The serum osteoprotegerin level in patients with Gensini score 20-40 scores was significantly higher than that in patients with Gensini score ＜ 20 scores,and there was statistical difference (P ＜0.05).The serum osteoprotegerin level in single-vessel lesion (16 cases),double-vessel lesion (57 cases) and three-vessel lesion (35 cases) [(3.52 ± 0.82),(4.54 ± 0.68),(4.75 ±0.93) ng/L] were significantly higher than those in control group,and there were statistical differences (P ＜ 0.05); and the serum osteoprotegerin level in double-vessel lesion and three-vessel lesion were significantly higher than those in single-vessel lesion,and there were statistical differences (P ＜ 0.05) ;there was no statistical difference between three-vessel lesion and double-vessel lesion(P＞ 0.05).The results of Logistic regression analysis showed that glycosylated hemoglobin,total cholesterol,high sensitivity C reactive protein and osteoprotegerin were independent risk factors of type 2 DM complicated with CHD.Conclusions Serum osteoprotegerin level in patients with type 2 DM complicated with CHD is significantly increased.There is a significant association between serum osteoprotegerin level and the presence and severity of CHD,and the serum osteoprotegerin level is independent risk factors of type 2 DM complicated with CHD.