P2-248: CLASSIFYING DEMENTIA PROGRESSION USING INFLAMMATORY AND MICROBIAL PROFILING OF SALIVA

Saliva is a filtered peripheral biofluid, ideally suited for non-invasive biomarker monitoring. Recently, neuronal proteins and lactoferrin have been observed in Alzheimer's disease patient, emphasizing a link between systemic inflammation in response to microbial pathogens and neurodegenerative dementia. We addressed whether cytokine profiling and microbial load classify dementia progression. 70 subjects of both genders between the age of 65 and 82 years old were tested for cognition (MMSE) and olfaction (UPSIT). Whole unstimulated saliva was collected and used to perform ApoE genotyping, Aimplex multiplex assay and microbiome analysis. In the population with MMSE <26 (n=36), we observe a 48% incidence of ApoEe4 allele in contrast to the 23% of ApoEe4 allele in the group with an MMSE≥26 (n=34). UPSIT and MMSE scores positively correlate across the whole cohort (r=0.68, p<0.001). Multivariate PCA analysis based on the weighed ratio of UPSIT (UP) and MMSE (MM) scores identifies 4 population segments: hiUPSIT-hiMMSE, hiMMSE-loUPSIT (group considered at risk), loMMSE-hiUPSIT and loMMSE-loUPSIT. The cytokines’ analysis of saliva reveals that the inflammatory grade in the hiMMSE-hiUPSIT segment is the highest in aggregate as compared to the other segments. In particular, 4 cytokines of the innate immunity, IL-1a, IL-1b, IL-33 and IL-8 decline significantly between the hiMMSE-loUPSIT and the loMMSE-hiUPSIT segments representing a potential classifier for the two conditions (AUC=0.877, p<0.01). The salivary microbiome shows a progressive increase in Shannon diversity with the severity of the cognitive impairment and hyposmia. Phylum classification evidences that Spirochetes counts are reduced 4.1 folds in the loMMSE as compared to the hiMMSE group. Further, 3 species of the Spirochetes family appears differentially expressed between the hiMMSE-loUPSIT and the loMMSE-hiUPSIT group: Treponema zioleckii (3.9 folds, p<0.05), Treponema socranskii (3.8 folds, p<0.05), Treponema medium (3.3 fold, p<0.05) and 2 Clostridium species: Clostridium frigoris (2.3 fold, p<0.05) and Filifactor villosus (3.2 folds, p<0.05). The inflammatory grade decays with the progression of dementia, identified by olfactory and cognitive profiles, and the microbial flora changes with the onset of the cognitive symptoms. This data suggests that dysbiosis between pathogen and the host can reflect the transition from physiological to pathological brain aging.