Widespread transposable element dysregulation in human aging brains with Alzheimer's disease
Widespread transposable element (TE) dysregulations are observed in human aging brains with degrees of neuropathology, apolipoprotein E (APOE) genotypes, and neuroinflammation in Alzheimer's disease (AD). A catalog of TE quantitative trait loci (teQTLs) in human aging brains was created using matched RNA sequencing and whole-genome sequencing data. CRISPR interference assays reveal that an upregulated intergenic TE from the MIR family (chr11: 47608036-47608220) suppresses expression of its nearest anti-inflammatory gene C1QTNF4 in human induced pluripotent stem cell-derived neurons.
Authors
- Yuan Hou (ORCID: https://orcid.org/0000-0002-3900-6122)
- Yayan Feng (ORCID: https://orcid.org/0000-0002-3932-0779)
- Charis Eng (ORCID: https://orcid.org/0000-0002-3693-5145)
- Yin Shen (ORCID: https://orcid.org/0000-0001-8380-2428)
- Xiaoyu Yang (ORCID: https://orcid.org/0009-0001-0035-9289)
- Andrew A. Pieper (ORCID: https://orcid.org/0000-0001-6299-6577)
- Yadi Zhou (ORCID: https://orcid.org/0000-0002-6049-0545)
- Alison Goate (ORCID: https://orcid.org/0000-0002-0576-2472)
- James B. Leverenz
- Feixiong Cheng
Institutions
- Cleveland Clinic (US)
- University of California, San Francisco (US)
- Lou Ruvo Brain Institute (US)
- Cleveland Clinic Lerner College of Medicine (US)
- University Hospitals Cleveland Medical Center (US)
- Geriatric Research Education and Clinical Center (US)
- Louis Stokes Cleveland VA Medical Center (US)
- University School (US)
- Case Western Reserve University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2024-10-02
- DOI
- https://doi.org/10.1002/alz.14164
- Citations
- 7
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 4.20
Funders
- U.S. Department of Veterans Affairs
- Alzheimer's Association
- American Heart Association
- Alzheimer's Drug Discovery Foundation
- Illinois Department of Public Health
- Case Western Reserve University
- National Institute on Aging
- National Institute of Neurological Disorders and Stroke