Framingham Heart Data Suggests Alzheimer's Disease-Related Gene Expression Influenced by Obesity

For a paper appearing in Alzheimer's & Dementia, a team from UT Health San Antonio, Boston University School of Medicine, the Framingham Heart Study, and elsewhere turn to transcriptome data to analyze Alzheimer's disease-related genes, uncovering an apparent obesity association with expression levels for a subset of the genes. With clinical, demographic, and blood-based gene expression data more than 5,600 Framingham Heart Study participants, the researchers used a transcriptome-wide association study approach to track down dozens of genes with enhanced or muted expression in Alzheimer's disease. Body mass index (BMI) and waist-to-hip ratio (WHR) measures coincided with expression for 21 of the genes, including more than a dozen genes with significant ties to obesity metrics after adjusting for related cardiovascular traits. "After adjustment for cardiovascular risk factors, 14 associations remained significant, indicating that obesity might be modulating the expression of AD-related genes both directly and indirectly through vascular pathways," the authors report, including 10 genes with higher-than-usual obesity-related expression and four genes with dialed-down expression. "The present findings provide important insights into the mechanistic intermediates of the pathway leading from obesity to dementia," they suggest, noting that such results "could assist public health and dementia prevention policies to target lifestyle interventions, such as weight loss, to population groups that might have the most benefit."