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Published on: May 20, 2024
Allele specific expression in Alzheimer's disease
Zishan Wang1, Delowar Hossain2, Judy Jiaru Wang3
1Department of Genetics and Genomic Sciences, Center for Transformative Disease Modeling, Tisch Cancer Institute, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Summary
Allele-specific expression (ASE) is newly characterized in Alzheimer's disease (AD), revealing novel variants and cell-type-specific gene downregulation linked to disease pathogenesis.
Area of Science:
- Genomics
- Neuroscience
- Molecular Biology
Background:
- Allele-specific expression (ASE) is linked to brain diseases but not well understood in Alzheimer's disease (AD).
- Understanding ASE in AD is crucial for identifying novel disease mechanisms.
Purpose of the Study:
- To perform a genome-wide characterization of ASE variants in Alzheimer's disease (AD).
- To investigate the cell-type-specific activity of ASE variants in the brain.
Main Methods:
- Genome-wide analysis of ASE variants in 2,231 AD and control patients across seven brain regions.
- Single-cell analysis to determine cell-type-specific ASE activity.
Main Results:
- Identified 56,136 unique ASE variants, enriched in imprinted chromosomal regions and exons of AD-associated genes (e.g., APOE).
- Discovered 40 AD-associated ASE variants, with affected genes predominantly downregulated in astrocytes, excitatory neurons, and oligodendrocytes.
Conclusions:
- Provided a comprehensive landscape of ASE in Alzheimer's disease (AD).
- Uncovered novel functional ASE variants and their potential cell-type-specific roles in AD pathogenesis.
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