Areas Associated with Early Alzheimer’s Pathology Contain Predominantly Oral Bacteria

Objectives: There is compelling evidence to suggest a strong link between periodontitis and late onset Alzheimer’s disease (LOAD). This includes studies showing a relationship between periodontal health, including levels of circulating antibodies to periodontal pathogens, and cognitive impairment, as well as large-scale population studies. The aetiology of LOAD is known to have a large inflammatory component mediated by the innate immune system in the brain. Chronic peripheral inflammation such as that caused by periodontitis may have a role in activation of inflammatory processes in the brain and subsequent LOAD associated pathology, but additionally, the direct incursion of microbial pathogens, including periodontal bacteria, into the CNS may have an important role. Here, we have characterised bacterial populations found in post-mortem brain samples from areas relevant to early and late stages of AD pathology.
Methods: 16S ribosomal gene amplicon Next Generation Sequencing and quantitative PCR were used to survey bacterial populations in post-mortem brain tissue from LOAD and control individuals from a cohort of 29 controls and 41 AD subjects supplied by the South West Dementia Brain Bank, Bristol Medical School, UK.
Results: We provide evidence that there are bacterial populations in both LOAD and control brain tissue over and above that expected from the blood content of the brain and post-mortem processes. Furthermore, the bacterial composition present in brain areas associated with the earlier stages of disease progression may be different to areas associated with later stages. This contrast may be characterised by higher relative levels of almost exclusively oral bacteria, including, both recognised oral pathogens and commensals, in those areas associated with early pathology.
Conclusions: Sub-cortical areas of the brain contain a wide spectrum of bacterial species predominantly associated with the oral microbiome and periodontitis. Fewer bacteria were found in cortical regions and contained skin commensals from the actinobacteria and proteobacteria of possible gut origin as well as oral species.