Long-read transcript sequencing identifies differential isoform expression in the entorhinal cortex in a transgenic model of tau pathology.
Nat Commun
; 15(1): 6458, 2024 Aug 02.
Article
en En
| MEDLINE
| ID: mdl-39095344
ABSTRACT
Increasing evidence suggests that alternative splicing plays an important role in Alzheimer's disease (AD) pathology. We used long-read sequencing in combination with a novel bioinformatics tool (FICLE) to profile transcript diversity in the entorhinal cortex of female transgenic (TG) mice harboring a mutant form of human tau. Our analyses revealed hundreds of novel isoforms and identified differentially expressed transcripts - including specific isoforms of Apoe, App, Cd33, Clu, Fyn and Trem2 - associated with the development of tau pathology in TG mice. Subsequent profiling of the human cortex from AD individuals and controls revealed similar patterns of transcript diversity, including the upregulation of the dominant TREM2 isoform in AD paralleling the increased expression of the homologous transcript in TG mice. Our results highlight the importance of differential transcript usage, even in the absence of gene-level expression alterations, as a mechanism underpinning gene regulation in the development of AD neuropathology.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ratones Transgénicos
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Proteínas tau
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Corteza Entorrinal
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Isoformas de Proteínas
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Enfermedad de Alzheimer
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido