2023 Alzheimer's Association Research Grant (AARG)
High-spatial-resolution Sequencing to Study Alzheimer's Disease
How does gene activity change in different parts of the brain during Alzheimer’s?
Yanxiang Deng, Ph.D.
The Trustees of the University of Pennsylvania
Philadelphia, PA - United States
Background
Dr. Yanxiang Deng and colleagues have developed a new technology to help map gene activity onto biological tissue samples. The technology, called deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq) can help researchers understand where in the brain certain genes are turned “on” or “off.” Dr. Deng’s team has tested this technique in brain tissue samples collected from individuals who had Alzheimer’s and in mice genetically engineered to have an Alzheimer’s-like disease. This approach has enabled Dr. Deng to measure gene activity inside certain brain regions affected by Alzheimer’s, including the prefrontal cortex and hippocampus. Dr. Deng is also studying how epigenetic modification, or the chemical modification of genetic material, influences gene activity in these brain regions.
Research Plan
For this study, Dr. Deng’s team will perform advanced gene sequencing techniques, including DBiT-seq, in brain tissue samples donated by individuals who had Alzheimer’s. The researchers will measure gene activity in the samples. They will create maps of the tissue samples that show where different genes are active. They will also use advanced computational techniques known as “-omics” to overlay other types of gene activity onto the maps. In total, the comprehensive maps will include gene sequences, transcriptomics (how gene activity is turned “on” or “off” within a cell), and epigenomics (chemical modification of genes). Dr. Deng will compare the brain tissue maps of individuals with Alzheimer’s to older adults without Alzheimer’s to understand the differences. This will allow Dr. Deng to understand exactly how – and where – gene activity changes in the brain during Alzheimer’s.
Impact
This study will develop new, advanced genetic analyses to understand exactly how genes are activated in the brain during Alzheimer’s. The DBiT-seq technique could also be used by other researchers who are interested in mapping gene activity in biological samples.