Targeted plasma proteome, transcriptome, and e/pQTL analyses identify potential novel biomarkers for Alzheimer's disease in African Americans
- PI
- Carrasquillo, Minerva
- DAR ID
- 12087
- Initial Approval Date
- February 3, 2026
- Current DAR Status
- Active
- PI Institution
- Mayo Clinic Florida
- PI Institution Country
- United States
- PI Institution Type
- Non-Profit
Requested Datasets (2)
Research Use Statement
The objective of this study is to identify genetic variants that influence plasma levels of transcripts and proteins that could serve as diagnostic blood-based biomarkers of Alzheimer’s disease in African Americans.
Plasma samples were collected from the Florida Consortium of African Americans Alzheimer’s disease studies (FCA3DS). Targeted DNA sequencing was performed across ten Alzheimer’s disease-associated loci to assess genetic variation. Plasma transcript levels and total tau protein concentrations were previously measured in this cohort using a custom nanoString panel and Simoa assays. Plasma proteome data were generated using the SomaScan 7k platform. Phased haplotypes generated with SHAPEIT4 were used to infer local ancestry via RFMix v2, referencing five superpopulations from the 1000 Genomes Project. Using ancestry-specific allelic dosages estimated with Tractor, association testing was conducted between genetic variants and molecular endophenotypes. Receiver operating characteristic analysis was performed to evaluate the additive classification accuracy of age, sex, and the most significant expression/protein QTLs in distinguishing Alzheimer’s disease cases from cognitively unimpaired controls.
We plan to utilize the requested dataset to validate our findings as these datasets include plasma proteome measurements, pQTL summary statistics, and plasma cell free RNA transcriptomics from healthy control, presymptomatic AD, early symptomatic AD, and symptomatic AD participants.
Plasma samples were collected from the Florida Consortium of African Americans Alzheimer’s disease studies (FCA3DS). Targeted DNA sequencing was performed across ten Alzheimer’s disease-associated loci to assess genetic variation. Plasma transcript levels and total tau protein concentrations were previously measured in this cohort using a custom nanoString panel and Simoa assays. Plasma proteome data were generated using the SomaScan 7k platform. Phased haplotypes generated with SHAPEIT4 were used to infer local ancestry via RFMix v2, referencing five superpopulations from the 1000 Genomes Project. Using ancestry-specific allelic dosages estimated with Tractor, association testing was conducted between genetic variants and molecular endophenotypes. Receiver operating characteristic analysis was performed to evaluate the additive classification accuracy of age, sex, and the most significant expression/protein QTLs in distinguishing Alzheimer’s disease cases from cognitively unimpaired controls.
We plan to utilize the requested dataset to validate our findings as these datasets include plasma proteome measurements, pQTL summary statistics, and plasma cell free RNA transcriptomics from healthy control, presymptomatic AD, early symptomatic AD, and symptomatic AD participants.
Non-Technical Summary
African Americans are historically underrepresented in Alzheimer’s disease research and may have disproportionately limited access to neurology clinics where Alzheimer’s disease is often diagnosed and treated. Blood-based biomarkers could offer a means for patients to obtain accessible and accurate diagnostic information related to Alzheimer’s disease. This study seeks to discover novel blood-based biomarkers to aid in diagnosis of Alzheimer’s disease specifically for African Americans.
Reported Publications
Publications shown are those reported by investigators through NIAGADS DAR reporting and renewal processes and may not represent a complete list of publications associated with the project.
No publications have been reported for this DAR.