The Correlations Between Plasma Fibrinogen With Amyloid-Beta and Tau Levels in Patients With Alzheimer’s Disease

Fan, Dong-Yu; Sun, Hao‐Lun; Sun, Pu‐Yang; Jian, Jie-Ming; Li, Weiwei; Shen, Yujie; Zeng, Fan; Wang, Yan‐Jiang; Bu, Xian‐Le

doi:10.3389/fnins.2020.625844

Cited by 12 publications

(7 citation statements)

References 28 publications

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“…Fibrinogen is a glycoprotein that is mainly involved in coagulation, as well as vasoreactivity and vascular permeability, inducing endothelial dysfunction at high concentrations [ 105 ] ( Figure 2 ). In fact, plasma levels of fibrinogen are elevated in cardiovascular and cerebrovascular diseases [ 105 ], as well as in AD [ 106 ]; however, a later study found no significant differences in plasma levels of fibrinogen from AD samples compared to those in controls [ 107 ]. Despite this, correlations between fibrinogen levels and different AD biomarkers were found: (1) plasma concentration of fibrinogen was positively correlated with plasma concentration of Aβ 40 and Aβ 42 as well as CSF concentration of T-tau and p-tau-181, but negatively correlated with CSF concentration of Aβ 42 ; (2) plasma concentration of fibrinogen was positively correlated with T-tau/Aβ 42 and p-tau/Aβ 42 ratios [ 107 ] ( Table 2 ).…”

Section: Vascular Biomarkers In Admentioning

confidence: 99%

Biomarkers Assessing Endothelial Dysfunction in Alzheimer’s Disease

Custodia

Aramburu-Núñez

Rodríguez-Arrizabalaga

et al. 2023

Cells

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Alzheimer’s disease (AD) is the most common degenerative disorder in the elderly in developed countries. Currently, growing evidence is pointing at endothelial dysfunction as a key player in the cognitive decline course of AD. As a main component of the blood–brain barrier (BBB), the dysfunction of endothelial cells driven by vascular risk factors associated with AD allows the passage of toxic substances to the cerebral parenchyma, producing chronic hypoperfusion that eventually causes an inflammatory and neurotoxic response. In this process, the levels of several biomarkers are disrupted, such as an increase in adhesion molecules that allow the passage of leukocytes to the cerebral parenchyma, increasing the permeability of the BBB; moreover, other vascular players, including endothelin-1, also mediate artery inflammation. As a consequence of the disruption of the BBB, a progressive neuroinflammatory response is produced that, added to the astrogliosis, eventually triggers neuronal degeneration (possibly responsible for cognitive deterioration). Recently, new molecules have been proposed as early biomarkers for endothelial dysfunction that can constitute new therapeutic targets as well as early diagnostic and prognostic markers for AD.

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Section: Vascular Biomarkers In Admentioning

confidence: 99%

Biomarkers Assessing Endothelial Dysfunction in Alzheimer’s Disease

Custodia

Aramburu-Núñez

Rodríguez-Arrizabalaga

et al. 2023

Cells

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“…Increased fibrin(ogen) deposition has been observed in both blood vessels and the brain parenchyma of AD patients [ 105 , 111 ]. In addition, a recent study reported a positive correlation between plasma fibrinogen levels and Aβ and phosphorylated tau in the brains of AD patients [ 112 ]. However, two recent studies did not find a correlation between fibrinogen and AD risk or between brain deposition of fibrin(ogen) and Aβ or phosphorylated tau [ 113 , 114 ].…”

Section: The Fibrinolytic Systemmentioning

confidence: 99%

Vascular Dysfunction in Alzheimer’s Disease: Alterations in the Plasma Contact and Fibrinolytic Systems

Badimon

Torrente

Norris

2023

IJMS

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Alzheimer’s disease (AD) is the most common neurodegenerative disease, affecting millions of people worldwide. The classical hallmarks of AD include extracellular beta-amyloid (Aβ) plaques and neurofibrillary tau tangles, although they are often accompanied by various vascular defects. These changes include damage to the vasculature, a decrease in cerebral blood flow, and accumulation of Aβ along vessels, among others. Vascular dysfunction begins early in disease pathogenesis and may contribute to disease progression and cognitive dysfunction. In addition, patients with AD exhibit alterations in the plasma contact system and the fibrinolytic system, two pathways in the blood that regulate clotting and inflammation. Here, we explain the clinical manifestations of vascular deficits in AD. Further, we describe how changes in plasma contact activation and the fibrinolytic system may contribute to vascular dysfunction, inflammation, coagulation, and cognitive impairment in AD. Given this evidence, we propose novel therapies that may, alone or in combination, ameliorate AD progression in patients.

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“…For instance, blood-borne proteins such as prothrombin, thrombin, pKr-2, fibrinogen, and fibrin can activate microglia and induce neuroinflammation, resulting in neurodegeneration and cognitive decline in various animal models of AD [34,[42][43][44][45][46][47][48][49][50][51]. Moreover, some of these blood proteins (such as thrombin, fibrinogen, and fibrin) can cluster with Aβ, the main causal agent of AD, and can further exacerbate microglial activation [52][53][54][55][56]. Furthermore, fibrinogen deposition can lead to impaired memory and result in exacerbated levels of interleukin-6, ROS, mitochondrial superoxide, and nitrite in mouse brain neurons [57].…”

Section: Introductionmentioning

confidence: 99%

Pathophysiological Role of Microglial Activation Induced by Blood-Borne Proteins in Alzheimer’s Disease

et al. 2023

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The blood–brain barrier (BBB) restricts entry of neurotoxic plasma components, blood cells, and pathogens into the brain, leading to proper neuronal functioning. BBB impairment leads to blood-borne protein infiltration such as prothrombin, thrombin, prothrombin kringle-2, fibrinogen, fibrin, and other harmful substances. Thus, microglial activation and release of pro-inflammatory mediators commence, resulting in neuronal damage and leading to impaired cognition via neuroinflammatory responses, which are important features observed in the brain of Alzheimer’s disease (AD) patients. Moreover, these blood-borne proteins cluster with the amyloid beta plaque in the brain, exacerbating microglial activation, neuroinflammation, tau phosphorylation, and oxidative stress. These mechanisms work in concert and reinforce each other, contributing to the typical pathological changes in AD in the brain. Therefore, the identification of blood-borne proteins and the mechanisms involved in microglial activation and neuroinflammatory damage can be a promising therapeutic strategy for AD prevention. In this article, we review the current knowledge regarding the mechanisms of microglial activation-mediated neuroinflammation caused by the influx of blood-borne proteins into the brain via BBB disruption. Subsequently, the mechanisms of drugs that inhibit blood-borne proteins, as a potential therapeutic approach for AD, along with the limitations and potential challenges of these approaches, are also summarized.

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The Correlations Between Plasma Fibrinogen With Amyloid-Beta and Tau Levels in Patients With Alzheimer’s Disease

Cited by 12 publications

References 28 publications

Biomarkers Assessing Endothelial Dysfunction in Alzheimer’s Disease

Biomarkers Assessing Endothelial Dysfunction in Alzheimer’s Disease

Vascular Dysfunction in Alzheimer’s Disease: Alterations in the Plasma Contact and Fibrinolytic Systems

Pathophysiological Role of Microglial Activation Induced by Blood-Borne Proteins in Alzheimer’s Disease

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