1 SCIENTIFIC REPORTS | (2018) 8:16798 | DOI:10.1038/s41598-018-35009-y www.nature.com/scientificreports Correlative Light-Electron Microscopy detects lipopolysaccharide and its association with fbrin fbres in Parkinson’s Disease, Alzheimer’s Disease and Type 2 Diabetes Mellitus Greta M. de Waal 1 , Lize Engelbrecht 2 , Tanja Davis 1 , Willem J. S. de Villiers 1,3 , Douglas B. Kell 1,4,5 & Etheresia Pretorius 1 Many chronic diseases, including those classifed as cardiovascular, neurodegenerative, or autoimmune, are characterized by persistent infammation. The origin of this infammation is mostly unclear, but it is typically mediated by infammatory biomarkers, such as cytokines, and afected by both environmental and genetic factors. Recently circulating bacterial infammagens 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 signifcantly 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 thiofavin 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 fbrils may be observed. These data are consistent with the Iron Dysregulation and Dormant Microbes (IDDM) hypothesis in which bacterial infammagens such as LPS are responsible for anomalous blood clotting as part of the aetiology of these chronic infammatory diseases. Many chronic diseases, including those classifed as autoimmune, cardiovascular, or neurodegenerative, are asso- ciated with persistent infammation. Although typically mediated by ‘infammatory’ cytokines and afected by both environmental and genetic factors, the origin of this infammation is mostly unclear. Since the recognition that most peptic ulcers, other than those caused by non-steroidal anti-infammatory drugs (NSAIDs), have a microbial basis 1,2 , there is a signifcant body of literature that suggests many other supposedly non-communicable diseases might actually have a bacterial and/or viral origin. For instance, Herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochaetes are specifc microbes that have been implicated in the aetiology of Alzheimer’s Disease (AD) 3–14 . A bacterial link has also been suggested for Parkinson’s Disease (PD) 3,15–21 , and microbes have been associated with ageing in general 22 . The presence of an aberrant blood microbiome, as assessed by sequencing, has also been implicated in Type 2 Diabetes (T2D) and cardiovascular events 23–25 . 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. Correspondence and requests for materials should be addressed to E.P. (email: resiap@sun.ac.za) Received: 26 July 2018 Accepted: 27 October 2018 Published: xx xx xxxx OPEN