Cryptic exon inclusion is a molecular signature of LATE-NC in aging brains.
Acta Neuropathol
; 147(1): 29, 2024 02 03.
Article
in 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Dementia
/
TDP-43 Proteinopathies
/
Alzheimer Disease
Limits:
Humans
Language:
En
Journal:
Acta Neuropathol
Year:
2024
Type:
Article
Affiliation country:
United States