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Molecular Biology

Targeting hypercoagulation to alleviate Alzheimer’s disease progression in metabolic syndrome

Abstract

Introduction

Metabolic Syndrome (MetS) constitutes an important risk factor for Alzheimer’s disease (AD); however, the mechanism linking these two disorders has not been completely elucidated. Hence, hypercoagulation may account for the missing hallmark connecting MetS and AD. The present review proposes how hemostatic imbalance triggered in MetS advances in the context of AD. MetS causes interruption of insulin signaling and inflammation, inciting insulin resistance in the brain. Subsequently, neuroinflammation and brain endothelial dysfunction are prompted that further intensify the exorbitant infiltration of circulating lipids and platelet aggregation, thereby causing hypercoagulable state, impairing fibrinolysis and eventually inducing prothrombic state in the brain leading to neurodegeneration.

Objective

This study aims to understand the role of hypercoagulation in triggering the progression of neurodegeneration in MetS. It also offers a few interventions to prevent the progression of AD in MetS targeting hypercoagulation.

Methods

Literature studies based on MetS related neurodegeneration, the impact of coagulation on aggravating obesity and AD via the mechanisms of BBB disruption, neuroinflammation, and hypofibrinolysis.

Conclusion

The present paper proposes the hypothesis that hypercoagulation might amplify MetS associated insulin resistance, neuroinflammation, BBB disruption, and amyloid beta accumulation which eventually leads to AD.

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Fig. 1: Metabolic syndrome (MetS) triggered neurodegeneration via hypercoagulation.
Fig. 2: Schematic representation of pathogenesis of metabolic syndrome (MetS) linked Alzheimer’s disease (AD) via hypercoagulation.
Fig. 3

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Promotion of University Research and Scientific Excellence (PURSE), Department of Science & Technology (DST), Government of India, Ministry of Science & Technology, India and Indian Council of Medical Research (ICMR), Government of India, India

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SK, AKN, SP, SS, MA contributed in the conceptualization of the manuscript. SK, PK, SK, SS contributed in the writing of the manuscript.

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Correspondence to Abul Kalam Najmi.

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Khan, S., Pati, S., Singh, S. et al. Targeting hypercoagulation to alleviate Alzheimer’s disease progression in metabolic syndrome. Int J Obes (2021). https://doi.org/10.1038/s41366-021-00977-1

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