Genetic and socioeconomic modulation of biomarkers

Introduction Identification and measurement of biomarkers has become a key component of much research in the neurodegeneration field, particularly in research linking psychosocial stressors and brain health. Socioeconomic position may influence neurodegeneration through several pathways, including behaviors and psychosocial stress levels, both of which may influence biological markers of inflammation, coagulation, and adhesion. Underserved populations, particularly from low‐to‐middle‐income countries in Latin America (LMICs), are more likely to have experienced poor, chronic stress due to discrimination, limited educational and occupational opportunities, and minimal access to social support and health care. All of these factors can modify neurodegenerative disease risk and clinical progression of dementia, in part through changes in immune function. Complicating matters, few studies have characterized inflammatory biomarker levels in LMICs, where biological and environmental exposures likely modify immune profiles. Finally, the effect of complex genetic admixture on both baseline and disease‐associated inflammatory biomarker levels remains underexplored, greatly limiting the generalizability of dementia biomarkers (beta amyloid, tau, neurofilament) that were largely developed in homogenous populations. Method We propose to review the existing evidence and present our ongoing study fostered in the Multi‐Partner Consortium to Expand Dementia Research in Latin America (ReDLat) cohort divided into three groups: participants with Alzheimer´s Dementia (AD), participants with Frontotemporal Dementia (FTD), and controls. We will comprehensively assess gene and protein expression measures of immune function in blood to identify single and combined measurements that provide sensitive and specific distinction between AD and FTD and all cases from controls. In addition, we will assess the modulatory effect that social determinants of health (SDOH) have on these biological biomarkers. Expected Results Our expected outcome is to understand how SDOH contribute to gene and protein expression measures of immune function and how they modify the gold standard biomarkers of disease and risk for AD and FTD in Latin America. Conclusions New opportunities for identifying novel diagnostic and therapeutic inroads may be easier to detect in Latin American populations that display a greater environmental and genomic diversity, while simultaneously elucidating potential strategies f