ALZHEIMERS RESEARCH PROJECT: Collaborative genomic and transcriptomic profilling of MCI and AD cases using Whole Genome Sequencing, and single cell and spatial transcriptomics

National Institute On Aging

Investigators

Abstract

This collaborative project between the NIH Center for Alzheimer’s and Related Dementias (CARD), Vanderbilt University, and Rush University focuses on generating comprehensive genomic and transcriptomic datasets to investigate molecular differences across Alzheimer’s disease (AD), mild cognitive impairment (MCI), and no cognitive impairment (NCI). Whole genome sequencing is being conducted on 5,191 rigorously prioritized samples, selected based on the availability of detailed clinical data, MRI scans, and other relevant phenotypic information. This approach ensures the dataset’s high value for genome-wide association studies (GWAS) and downstream genetic analyses. In parallel, single-nucleus RNA sequencing (snRNA-seq) will be performed on 200 brain samples—67 from each of the AD, MCI, and NCI groups—to enable cell-type-specific profiling of gene expression. Spatial transcriptomics will also be conducted on 51 brain samples (17 per group) using Visium technology, allowing for spatial mapping of gene expression and correlation with pathological features. These experiments will include protein labeling to visualize disease-relevant markers within tissue architecture. Together, these efforts will produce a rich, multi-dimensional resource to support mechanistic insights and therapeutic discovery in Alzheimer's disease and related dementias.