Vascular Dementia and Crosstalk Between the Complement and Coagulation Systems

Abstract

Vascular Dementia (VaD) is a neurocognitive disorder caused by reduced blood flow to the brain tissue, resulting in infarction, and is the second most common type of dementia. The complement and coagulation systems are evolutionary host defence mechanisms activated by acute tissue injury to induce inflammation, clot formation and lysis; recent studies have revealed that these systems are closely interlinked. Overactivation of these systems has been recognised to play a key role in the pathogenesis of neurological disorders such as Alzheimer's disease and multiple sclerosis, however their role in VaD has not yet been extensively reviewed. This review aims to bridge the gap in knowledge by collating current understanding of VaD to enable identification of complement and coagulation components involved in the pathogenesis of this disorder that may have their effects amplified or supressed by crosstalk. Exploration of these mechanisms may unveil novel therapeutic targets or biomarkers that would improve current treatment strategies for VaD.

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“…Vascular dementia is caused by reduced blood supply to the brain due to vascular injury. Therefore, patients with cerebrovascular and cardiovascular disease are more likely to develop vascular dementia than normal individuals 47 . Unlike AD, no drug is clearly effective for vascular dementia, for which there is currently no approved treatment 45,48 .…”

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“…Small vessel disease (SVD) consists of different pathological findings such as small infarcts, microscopic infarcts, microbleeds, arteriolosclerosis, intracranial atherosclerosis, and cerebral amyloid angiopathy [119]. According to various studies, SVD is the most common cerebrovascular pathology found in examined samples of VaD patients [122][123][124]. In this respect, it is noticeable that SVD is associated with factors such as age, diabetes mellitus, hypertension and stroke, [125]and the key pathophysiological mechanisms underlying SVD are linked to ischemia, inflammation, and oxidative stress [124,126].…”

“…According to various studies, SVD is the most common cerebrovascular pathology found in examined samples of VaD patients [122][123][124]. In this respect, it is noticeable that SVD is associated with factors such as age, diabetes mellitus, hypertension and stroke, [125]and the key pathophysiological mechanisms underlying SVD are linked to ischemia, inflammation, and oxidative stress [124,126]. It has been demonstrated that following ischemia and inflammation, endothelial activation takes place.…”

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“…Moreover, bradykinin release by MASP-1 mediated cleavage of kininogen was demonstrated ( Dobo et al, 2011 ) and the enzyme that inactivates bradykinin is identical to the inactivator of the complement anaphylatoxins C3a and C5a ( Kaplan and Ghebrehiwet, 2010 ). Conversely, factor XII and XI may trigger complement activation ( Mossanen Parsi et al, 2021 ). Key elements of the KKS, the renin-angiotensin system and the coagulation system have been found to be co‐expressed with ACE2 in human alveolar cells ( Campbell and Kahwash, 2020 ).…”