1. Cryptic exon inclusion is a molecular signature of LATE-NC in aging brains.
- Author
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Chung M, Carter EK, Veire AM, Dammer EB, Chang J, Duong DM, Raj N, Bassell GJ, Glass JD, Gendron TF, Nelson PT, Levey AI, Seyfried NT, and McEachin ZT
- Subjects
- Humans, Brain pathology, Aging genetics, Aging pathology, DNA-Binding Proteins metabolism, Exons, TDP-43 Proteinopathies pathology, Alzheimer Disease genetics, Alzheimer Disease pathology, Dementia
- 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., (© 2024. The Author(s).)
- Published
- 2024
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