0099 Inflammatory Biomarkers and Sleep: Insights into Neurodegeneration and Alzheimer’s Disease in Diverse Populations

Abstract Introduction Sleep plays a vital role in maintaining brain health, supporting critical functions such as memory, toxin clearance, and neural repair. Sleep disruption increases the risk of Alzheimer’s disease (AD) and aging-related dementias. Neuroinflammation, driven by dysregulated sleep and aging, has emerged as a key contributor to AD pathology. Understanding specific inflammatory biomarkers, such as FKBP5, NRSF, IL-6, and TNF-α, in diverse populations may aid early diagnosis and intervention. We hypothesize that changes in the expression of these biomarkers are associated with aging and AD progression, providing insights into neuroinflammation and cognitive decline, particularly with sleep disturbances. Methods This study analyzed gene expression in frontal cortical regions of brain samples from individuals aged < 40 to 106 years, using publicly available data (GSE53890). Groups included young (< 40 years), middle-aged (40–70 years), normal-aged (70–94 years), extremely aged (95–106 years), and AD patients. We applied the Hallmark Inflammatory Response and Peptidyl Proline Modification Gene Sets to identify 292 inflammatory gene markers relevant to neuroinflammation. Biomarkers of inflammation (FKBP5, NRSF, IL-6, and TNF-α) were evaluated for their association with aging and AD. Linear regression and Spearman correlation analyses were conducted using GraphPad Prism to examine biomarker expression patterns. Results We analyzed gene expression patterns and identified significant changes in FKBP5, NRSF, IL-6, and TNF-α with aging and AD progression. FKBP5 expression was elevated in non-AD aging individuals (R²=0.5448), consistent with its role in inflammation regulation. NRSF expression remained stable with normal aging (R²=0.2793). Cytokine markers IL-6 and TNF-α were linked to advanced disease stages, suggesting their utility in tracking AD progression. Conclusion These findings underscore the potential of inflammatory biomarkers such as FKBP5, NRSF, IL-6, and TNF-α to enhance our understanding of aging and Alzheimer’s disease (AD) pathology. Our lab is actively conducting NIH-funded studies to further investigate these and other inflammatory markers within the context of sleep disturbances and AD risk. This research seeks to unravel the mechanisms underlying neuroinflammation and cognitive decline, with a particular focus on underrepresented Black and Latin-American populations, to promote health equity and inform the development of targeted interventions aimed at reducing AD risk. Support (if any)