Abstract
Alzheimer-type dementia (AD) is a neurodegenerative disorder and the most common form of dementia. Patients typically present with neuro- and systemic inflammation and iron dysregulation, associated with oxidative damage that reflects in hypercoagulability. Hypercoagulability is closely associated with increased fibrinogen and in AD patients fibrinogen has been implicated in the development of neuroinflammation and memory deficits. There is still no clear reason precisely why (a) this hypercoagulable state, (b) iron dysregulation and (c) increased fibrinogen could together lead to the loss of neuronal structure and cognitive function. Here we suggest an alternative hypothesis based on previous ultrastructural evidence of the presence of a (dormant) blood microbiome in AD. Furthermore, we argue that bacterial cell wall components, such as the endotoxin lipopolysaccharide (LPS) of Gram-negative strains, might be the cause of the continuing and low-grade inflammation, characteristic of AD. Here, we follow an integrated approach, by studying the viscoelastic and ultrastructural properties of AD plasma and whole blood by using scanning electron microscopy, Thromboelastography (TEG®) and the Global Thrombosis Test (GTT®). Ultrastructural analysis confirmed the presence and close proximity of microbes to erythrocytes. TEG® analysis showed a hypercoagulable state in AD. TEG® results where LPS was added to naive blood showed the same trends as were found with the AD patients, while the GTT® results (where only platelet activity is measured), were not affected by the added LPS, suggesting that LPS does not directly impact platelet function. Our findings reinforce the importance of further investigating the role of LPS in AD.
Highlights
Alzheimer-type dementia (AD) is a neurodegenerative disorder and the most common form of dementia [1,2,3]
Results from the Global Thrombosis Test (GTT)® showed that added LPS did not have an effect on platelet shear force in the GTT®
In the current sample we see that the following parameters were significantly different between healthy and Alzheimer-type dementia individuals:
Summary
Alzheimer-type dementia (AD) is a neurodegenerative disorder and the most common form of dementia [1,2,3]. Dementia is a syndrome applied to a group of symptoms that can be caused by a variety of conditions, the most common of which is Alzheimer’s disease; due in part to this ambiguity, the aetiology of AD is not well understood [4]. Neuroinflammation is a multi-faceted and complex phenomenon where the precise mechanisms have not been completely elucidated [10], but where activated astrocytes and microglia are usually the trigger in the neuroinflammatory process. They become reactive in www.impactjournals.com/oncotarget response to virtually all pathological situations in the brain such as axotomy (neuritic dystrophy), ischemia, infection, and existing neurodegenerative diseases [11,12,13,14,15]
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