정민기 (Emory University)

한빛사논문

조회196

정민기Mingee Chung

Emory University

Acta Neuropathol., Feb 03 2024, 147 (1) | https://doi.org/10.1007/s00401-023-02671-0 Cryptic exon inclusion is a molecular signature of LATE-NC in aging brains

Mingee Chung^1,2, E. Kathleen Carter³, Austin M. Veire⁴, Eric B. Dammer³, Jianjun Chang¹, Duc M. Duong³, Nisha Raj^1,2,5, Gary J. Bassell^1,2,6, Jonathan D. Glass^6,7, Tania F. Gendron^4,8, Peter T. Nelson⁹, Allan I. Levey^6,7, Nicholas T. Seyfried^3,6, Zachary T. McEachin^1,2,5,6

¹Department of Cell Biology, Emory University, Atlanta, GA 30322, USA

²Laboratory for Translational Cell Biology, Emory University, Atlanta, GA 30322, USA

³Department of Biochemistry, Emory University, Atlanta, GA 30322, USA

⁴Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA

⁵Department of Human Genetics, Emory University, Atlanta, GA 30322, USA

⁶Center for Neurodegenerative Diseases, Emory University, Atlanta, GA 30322, USA

⁷Department of Neurology, Emory University, Atlanta, GA 30322, USA

⁸Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA

⁹Department of Pathology and Sanders-Brown Center On Aging, University of Kentucky, Lexington, KY 40536, USA

Corresponding authors

Correspondence to Allan I. Levey, Nicholas T. Seyfried or Zachary T. McEachin.

Abstract

The aggregation, mislocalization, and phosphorylation of TDP-43 are pathologic hallmarks of several neurodegenerative diseases and provide a defining criterion for the neuropathologic diagnosis of Limbic-predominant Age-related TDP-43 Encephalopathy (LATE). LATE neuropathologic changes (LATE-NC) are often comorbid with other neurodegenerative pathologies including Alzheimer's disease neuropathologic changes (ADNC). We examined whether TDP-43 regulated cryptic exons accumulate in the hippocampus of neuropathologically confirmed LATE-NC cases. We found that several cryptic RNAs are robustly expressed in LATE-NC cases with or without comorbid ADNC and correlate with pTDP-43 abundance; however, the accumulation of cryptic RNAs is more robust in LATE-NC with comorbid ADNC. Additionally, cryptic RNAs can robustly distinguish LATE-NC from healthy controls and AD cases. These findings expand our current understanding and provide novel potential biomarkers for LATE pathogenesis.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-06)
연구진국외 연구진
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