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Sci Rep. 2018 Nov 14;8(1):16798. doi: 10.1038/s41598-018-35009-y.

Correlative Light-Electron Microscopy detects lipopolysaccharide and its association with fibrin fibres in Parkinson's Disease, Alzheimer's Disease and Type 2 Diabetes Mellitus.

Author information

1
Department of Physiological Sciences, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland, 7602, South Africa.
2
Central Analytical Facilities, Fluorescence Microscopy Unit, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland, 7602, South Africa.
3
Department of Internal Medicine, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland, 7602, South Africa.
4
School of Chemistry, The University of Manchester, 131 Princess St, Manchester, Lancs, M1 7DN, UK.
5
Manchester Institute of Biotechnology, The University of Manchester, 131 Princess St, Manchester, Lancs, M1 7DN, UK.
6
Department of Physiological Sciences, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland, 7602, South Africa. resiap@sun.ac.za.

Abstract

Many chronic diseases, including those classified as cardiovascular, neurodegenerative, or autoimmune, are characterized by persistent inflammation. The origin of this inflammation is mostly unclear, but it is typically mediated by inflammatory biomarkers, such as cytokines, and affected by both environmental and genetic factors. Recently circulating bacterial inflammagens such as lipopolysaccharide (LPS) have been implicated. We used a highly selective mouse monoclonal antibody to detect bacterial LPS in whole blood and/or platelet poor plasma of individuals with Parkinson's Disease, Alzheimer's type dementia, or Type 2 Diabetes Mellitus. Our results showed that staining is significantly enhanced (P < 0.0001) compared to healthy controls. Aberrant blood clots in these patient groups are characterized by amyloid formation as shown by the amyloid-selective stains thioflavin T and Amytracker™ 480 or 680. Correlative Light-Electron Microscopy (CLEM) illustrated that the LPS antibody staining is located in the same places as where amyloid fibrils may be observed. These data are consistent with the Iron Dysregulation and Dormant Microbes (IDDM) hypothesis in which bacterial inflammagens such as LPS are responsible for anomalous blood clotting as part of the aetiology of these chronic inflammatory diseases.

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