Impact of the Coagulation System on the Pathogenesis of Alzheimer's Disease

Alzheimer's disease (AD) leads to cognitive impairment and is eventually fatal. The cognitive decline is associated with extensive neuronal degeneration. The most well-known pathological features of AD are extracellular Aβ plaques, intracellular tau tangles, neuroinflammation, and neuronal loss. Less discussed is that AD is often associated with cerebrovascular abnormalities. The symptoms of AD and cerebrovascular pathology could be independent co-morbidities, with both being increased in aging populations. However, it is also possible that there is a mechanistic link between AD and vascular pathology. The interaction of Aβ with fibrin(ogen) can lead to increased fibrin deposition in cerebral blood vessels, and these accumulated fibrin deposits may disrupt cerebral blood flow and induce microinfarcts, inflammation, and BBB damage, all of which are aspects of cerebrovascular dysfunction observed in AD. At the same time, Ab's ability to activate FXII may contribute to increased fibrin generation through the intrinsic coagulation pathway as well as to increased inflammation and vascular permeability through bradykinin release from HK. These possible roles of Aβ in thrombosis, fibrinolysis, and inflammation via its interaction with fibrinogen and FXII, summarized in Figure 1, will be discussed.