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Acta Neuropathol ; 147(1): 29, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308693

RESUMO

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.


Assuntos
Doença de Alzheimer , Demência , Proteinopatias TDP-43 , Humanos , Encéfalo/patologia , Proteinopatias TDP-43/patologia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Envelhecimento/genética , Envelhecimento/patologia , Proteínas de Ligação a DNA/metabolismo , Éxons
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