Basic Science and Pathogenesis

Area of Science:

• Neuroscience
• Genomics
• Epigenetics

Background:

• Sporadic Alzheimer's disease (AD) is a complex condition hindering therapeutic development.
• Understanding cell-specific molecular changes in AD progression is crucial for identifying therapeutic targets.

Purpose of the Study:

• To investigate molecular changes in specific brain cell types during sporadic Alzheimer's disease progression.
• To identify novel therapeutic targets by analyzing gene expression and epigenetic modifications.

Main Methods:

• Utilized NETSseq technology for deep gene expression and paired epigenetic profiling of human post-mortem brain tissue.
• Applied NETSseq to control, early-, and late-sporadic AD donor samples, generating astrocyte RNA-seq and ATAC-seq data.

Main Results:

• Correlated RNA-seq and ATAC-seq data to identify regulatory regions and their target genes within cell types.
• Discovered significant chromatin and gene expression changes in astrocytes during AD progression.
• Linked genomic data with GWAS AD data, validating known associations and identifying novel astrocyte-specific targets.

Conclusions:

• NETSseq provides reproducible molecular profiles of CNS cell types.
• Enables understanding of temporal dynamics in chromatin and gene expression during disease.
• Identifies relevant pathways and genes for novel therapeutic strategies in Alzheimer's disease.