Blood-Based Identification and Analysis of Sex-Specific Biomarkers in Alzheimer’s Disease
Alzheimer’s Disease (AD) is the sixth leading cause of death in the United States. Despite studies demonstrating that females having a greater lifetime risk of developing AD, molecular signatures underlying these findings remain elusive. Current detection methods such as neuroimaging and cerebrospinal fluid analysis are invasive and costly, and thus, inaccessible to many. To develop a more affordable diagnostic, I conducted a comprehensive, sex-specific meta-analysis of whole blood gene expression in the context of AD. I elucidated a female-specific gene expression signature using network-based approaches, validated in part by a sex-stratified Genome Wide Association Study (GWAS). I analyzed three publicly available microarray datasets, revealing female-specific AD gene signatures involving immune-related processes. These findings were confirmed by the upregulation of specific immune cell types in affected females, as well as Single Nucleotide Polymorphisms found in immune-related genes via the sex-stratified GWAS. Network- and cell type-specific analyses revealed biological functions that specifically affect females only, offering a novel transcriptomic explanation for differential AD risk across sexes. Our findings represent the largest analysis of whole blood gene expression in AD to date and provide a critical step forward towards understanding sex differences in AD. These findings should inform the development of more personalized and effective blood-based diagnostics for AD.
Aarzu Gupta is a senior at The Harker School in San Jose, CA, and a STEM enthusiast. In addition to being an extremely passionate researcher in the intersection of Biology and Computer Science, she is the president of the WiSTEM club, Co-editor and chief for the Harker Horizon magazine, and a member of Harker’s robotics team, specifically in the field of CAD. Aside from her STEM interests, she loves to sing, dance, and support the education of others. She is able to fulfill these hobbies through performing in a women’s chamber chorus, running a Bollywood dance team, and holding workshops for younger girls, helping them create projects combining music, engineering, and code through a non-profit she initiated called MusiCodes.