![]() 16S RDNA SEQUENCE ANALYSIS FREEAll brain samples are routinely assessed by the South West BB for prion disease only brain samples from subjects free of prion disease pathology were released for this study. All studies conformed to relevant regulatory standards. Materials and Methods Cohort Studyįrozen and paraffin embedded tissue was obtained, with local Research Ethics Committee approval, from the South West Dementia Brain bank (SWDBB), University of Bristol, UK. Here we use 16S ribosomal RNA gene next generation sequencing (NGS) in a pilot comparative study in normal and AD-affected brains to determine the range and extent of bacterial species present in this brain tissue. The evidence so far is reliant on histology and other methods that require prior knowledge of which bacterial species to look for. Evidence suggests that the influence of neuroinflammation is involved at an early stage of AD ( Akiyama et al., 2000b Holmes et al., 2009 Perry et al., 2010 Perry and Holmes, 2014) and it has been demonstrated that a microbiological insult, including bacteria or virus, may trigger, or contribute to neuroinflammation and subsequent neurological damage ( Miklossy, 2011 Mawanda and Wallace, 2013 Hill et al., 2014 Cerajewska et al., 2015 Olsen and Singhrao, 2015, 2016 Shoemark and Allen, 2015 Itzhaki et al., 2016 Miklossy and McGeer, 2016). The polymorphisms found by these studies to be associated with AD are thought to mainly affect three functional systems: immune and inflammation responses, lipid metabolism and endosomal vesicle recycling ( Tosto and Reitz, 2013 Guerreiro and Hardy, 2014). Further to this, multicenter genome-wide association studies (GWAS) have identified susceptibility loci on genes which may increase or decrease the risk of AD ( Bertram and Tanzi, 2009). The E4 polymorphism is proinflammatory, unlike the more common E3 form, which facilitates suppression of inflammation ( LaDu et al., 2001 Guo et al., 2004 Chen et al., 2005). One reason for this is likely to be its importance in the clearance of Aβ, another may be its influence on inflammatory response and its adverse influence on the integrity of the blood-brain barrier (BBB Bell, 2012), which is pertinent when discussing the level of privilege the brain retains ( Yu et al., 2014). The presence of the E4 polymorphism of apolipoprotein E4 ( APOE4) has long been known to be the most potent risk factor for sporadic AD, second only to age. The common sporadic form of AD arises from a large number of possible risk factors. However, understanding why the presence of excessive levels of Aβ do not necessarily result in cognitive impairment ( Katzman et al., 1988 Hulette et al., 1998 Price and Morris, 1999 Aizenstein et al., 2008 Esparza et al., 2013) may be related to the known role of inflammation and the importance of the response of the innate immune system, which are also recognized as essential factors ( Heneka et al., 2015b). It is acknowledged that the increased level of amyloid Aβ42 in the brain parenchyma, due to either increased production of amyloid or its decreased removal, is likely to contribute substantially to this. Pathological triggers, culminating in the eventual loss of cognitive function in Alzheimer’s disease (AD), are widely acknowledged to occur up to two decades before symptoms arise ( Bateman et al., 2012). Our findings suggest an increase in bacterial populations in Alzheimer brain tissue compared with normal. A comparison was made of the bacterial species content of both frozen and formaldehyde fixed sections of a small cohort of Alzheimer-affected cases with those of cognitively unimpaired (normal). This is a novel study using 16S ribosomal gene-specific Next generation sequencing (NGS) of extracted brain tissue. It is now being considered that microbiological incursion into the central nervous system could be either an initiator or significant contributor to these. Recently the tenet of the privileged status of the brain, regarding microbial compromise, has been questioned, particularly in terms of neurodegenerative diseases. This is now seen to be a significant contributor to pathology. The neurological deterioration associated with Alzheimer’s disease (AD), involving accumulation of amyloid-beta peptides and neurofibrillary tangles, is associated with evident neuroinflammation. 4School of Oral and Dental Sciences, Bristol, United Kingdom.3School of Biological Sciences, Life Sciences, University of Bristol, Bristol, United Kingdom.2School of Biochemistry, University Walk, Bristol, United Kingdom.1School of Clinical Sciences, Faculty of Health Sciences, University of Bristol, Bristol, United Kingdom. ![]()
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