Cryptic exon inclusion is a molecular signature of LATE-NC in aging brains.

Autor: Chung M; Department of Cell Biology, Emory University, Atlanta, GA, 30322, USA.; Laboratory for Translational Cell Biology, Emory University, Atlanta, GA, 30322, USA., Carter EK; Department of Biochemistry, Emory University, Atlanta, GA, 30322, USA., Veire AM; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA., Dammer EB; Department of Biochemistry, Emory University, Atlanta, GA, 30322, USA., Chang J; Department of Cell Biology, Emory University, Atlanta, GA, 30322, USA., Duong DM; Department of Biochemistry, Emory University, Atlanta, GA, 30322, USA., Raj N; Department of Cell Biology, Emory University, Atlanta, GA, 30322, USA.; Laboratory for Translational Cell Biology, Emory University, Atlanta, GA, 30322, USA.; Department of Human Genetics, Emory University, Atlanta, GA, 30322, USA., Bassell GJ; Department of Cell Biology, Emory University, Atlanta, GA, 30322, USA.; Laboratory for Translational Cell Biology, Emory University, Atlanta, GA, 30322, USA.; Center for Neurodegenerative Diseases, Emory University, Atlanta, GA, 30322, USA., Glass JD; Center for Neurodegenerative Diseases, Emory University, Atlanta, GA, 30322, USA.; Department of Neurology, Emory University, Atlanta, GA, 30322, USA., Gendron TF; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL, 32224, USA., Nelson PT; Department of Pathology and Sanders-Brown Center On Aging, University of Kentucky, Lexington, KY, 40536, USA., Levey AI; Center for Neurodegenerative Diseases, Emory University, Atlanta, GA, 30322, USA. alevey@emory.edu.; Department of Neurology, Emory University, Atlanta, GA, 30322, USA. alevey@emory.edu., Seyfried NT; Department of Biochemistry, Emory University, Atlanta, GA, 30322, USA. nseyfri@emory.edu.; Center for Neurodegenerative Diseases, Emory University, Atlanta, GA, 30322, USA. nseyfri@emory.edu., McEachin ZT; Department of Cell Biology, Emory University, Atlanta, GA, 30322, USA. zmceach@emory.edu.; Laboratory for Translational Cell Biology, Emory University, Atlanta, GA, 30322, USA. zmceach@emory.edu.; Department of Human Genetics, Emory University, Atlanta, GA, 30322, USA. zmceach@emory.edu.; Center for Neurodegenerative Diseases, Emory University, Atlanta, GA, 30322, USA. zmceach@emory.edu.
Jazyk: angličtina
Zdroj: Acta neuropathologica [Acta Neuropathol] 2024 Feb 03; Vol. 147 (1), pp. 29. Date of Electronic Publication: 2024 Feb 03.
DOI: 10.1007/s00401-023-02671-0
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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