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Oncotarget. 2015 Nov 3;6(34):35284-303. doi: 10.18632/oncotarget.6074.

Viscoelastic and ultrastructural characteristics of whole blood and plasma in Alzheimer-type dementia, and the possible role of bacterial lipopolysaccharides (LPS).

Author information

1
Department of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia, South Africa.
2
School of Chemistry and The Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK.

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.

KEYWORDS:

Alzheimer-type dementia; Gerotarget; iron levels; lipopolysaccharides; scanning electron microscopy; thromboelastography

PMID:
26462180
PMCID:
PMC4742105
DOI:
10.18632/oncotarget.6074
[Indexed for MEDLINE]
Free PMC Article

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