Cryptic exon inclusion is a molecular signature of LATE-NC in aging brains.
Acta Neuropathol
; 147(1): 29, 2024 02 03.
Article
em En
| MEDLINE
| ID: mdl-38308693
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Demência
/
Proteinopatias TDP-43
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Doença de Alzheimer
Limite:
Humans
Idioma:
En
Revista:
Acta Neuropathol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos