TMED11 Conference
Shaping Future Healthcare with Clinical Research and Personalised Prescribing
Join us at the historic Guildhall, Derry-Londonderry for the 11th TMED Conference – a leading international event in translational medicine bringing together clinical researchers, academics, industry partners and healthcare innovators from across the UK and Europe.
Poster 15- The role of the nlrp3 inflammasome in patients with alzheimer's disease and mild cognitive impairment: findings from plasma proteomic analyses in the UK biobank, adni and a Northern Irish cohort
Authors: McNaugher, G., McClean, P., Gibson, D., Murray, E. and McGilligan, V.
Affiliations: Personalised Medicine Centre, School of Medicine, Ulster University, Altnagelvin Hospital, Derry~Londonderry, Northern Ireland, UK
Background/ Introduction: Many studies have investigated the plasma proteomic profiles of individuals with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), consistently reporting altered levels of inflammatory markers. Among these pathways, the NLRP3 inflammasome has emerged as a potential contributor to AD pathology; however, its role in disease progression and cognitive decline is yet to be fully deduced.
Material & Methods: Plasma proteomic profiles for individuals with dementia, including AD, MCI and Dementia with Lewy bodies (DLB) were quantified using the Olink Target 96 and Explore 3072 platforms in a Northern Irish cohort and the UK Biobank whilst the Luminex-xMAP platform quantified plasma proteins within the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Differential abundance analyses were performed Student’s t-test and regression models used to adjust for age and sex. Enrichment analysis was used to identify molecular pathways implicated. To interrogate this further, we extracted outcomes for NLRP3 inflammasome related proteins, identified via STRINGdb, and employed Kaplan-Meier curves to investigate their impact on cognitive decline.
Results: Seven NLRP3-related proteins exhibited differential abundance in individuals with Alzheimer’s disease across both the UK Biobank and NI cohort. Following adjustment for age and sex, several proteins remained significantly altered (FDR < 0.05). After stratifying UKB participants into ‘high’ and ‘low’ protein groups using the Youden index, we found that individuals with elevated IL1R1 levels had a significantly increased probability of cognitive decline (p <0.00015) whilst other NLRP3-related proteins such as IL-18 (p <0.005), CCL2 (p =0.00059) and IL-1RN (p = 0.038) were associated with reduced risk, suggesting potential protective roles.
Conclusion: Plasma proteomic signatures related to the NLRP3 inflammasome may serve as promising biomarkers for predicting cognitive decline and offer prospective therapeutic targets for AD.
