Microbiome and AD/ADRD Risk in SOL

Project Summary/Abstract Alzheimer’s disease and related dementias (AD/ADRD) is a growing public health burden, further accentuated by the rapid aging of the US population and increased life expectancy. The gut microbiome, sometimes called the ‘second brain’ engages in bi-directional communication with the Central Nervous System (CNS) and is thought to contribute to neurodegeneration and AD/ADRD risk. The microbiome is dynamic, responsive to external stimuli and modifiable, creating the possibility for AD/ADRD prevention and treatment. Prior human studies on GMB and ADRD have had limitations such as cross-sectional design, small sample size, and lack of detailed GMB characterization. Notably few GMB and no GMB – AD/ADRD studies have focused on Latinos, a high-risk population, with distinct GMB profiles and over double the risk of AD/ADRD compared to non-Latino Whites. The proposed project will elucidate the microbial origins of AD/ADRD in SOL and examine whether the microbiome is a potential mechanism that links diabetes and AD/ADRD risk. We will use the SOL cohort’s AD/ADRD sub-study, which over ~15 years followed 6,377 individuals with longitudinal cognitive function assessments, structural brain MRI, plasma amyloid, Tau, and neurodegeneration (ATN) biomarkers (amyloid beta [AB40-42], p-tau181, neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP]), and plasma metabolomics. GMB metagenomic profiles are available among 2204 participants and longitudinal stool metagenomic and serum metabolomic profiles will be generated by this study. The study will benefit from careful assessment of key microbiome covariates, notably, medication, diet, anthropometric variables, physical activity, social and psychosocial factors. The proposed work will pave the path for GMB-based early detection, prevention and/or treatment of AD/ADRD among high-risk Latinos.