Hidden RNA Alterations by Jumping Genes in Alzheimer's Disease
Principal Investigator
Yuyun Zhang, PhD
University of California, Los Angeles
Los Angeles, CA, United States
About the Research Project
Program
Award Type
Standard
Award Amount
$25,000
Active Dates
July 01, 2026 - June 30, 2027
Grant ID
CA2026005
Acknowledgement
Mentor(s)
Xinshu (Grace) Xiao, PhD, University of California, Los Angeles
Goals
This project uncovers a hidden layer of RNA dysregulation driven by transposable elements and links it to genetic risk and pathology in Alzheimer’s disease.
Unique and Innovative
This proposal is, to our knowledge, the first systematic investigation of TE exonization as a distinct molecular mechanism in AD, moving beyond TE expression surveys to examine how TE-derived exons alter the coding and regulatory potential of disease-relevant genes. By integrating large-scale multi-cohort transcriptomics with whole-genome sequencing and AD GWAS, we introduce teiQTLs as a new class of functional variants linking noncoding genetic risk to RNA processing. This framework opens a new dimension of AD biology and provides a foundation for future biomarker and therapeutic strategies.
Foreseeable Benefits
Establishing TE exonization as a contributor to AD pathology will expand our understanding of the disease beyond established mechanisms, potentially revealing new targets for RNA-based therapies such as antisense oligonucleotides. The TE exon burden score developed in this study could serve as a molecular biomarker to stratify patients by disease stage or progression risk. More broadly, this work establishes a generalizable framework for studying TE exonization in other neurodegenerative diseases, benefiting the wider field of neurogenomics.