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Lack of association between TDP-43 pathology and tau mis-splicing in Alzheimer's disease.


ABSTRACT: A proportion of Alzheimer's disease cases displays inclusions of the RNA-binding protein, TDP-43. Considering the pathogenic role of tau mis-splicing, we compared tau isoform expression between Alzheimer's disease cases with or without TDP-43 inclusions. The average ratio of tau isoforms containing or lacking exon 10 (4R/3R ratio) or the total level of tau mRNA was not significantly different between cases with or without TDP-43 pathology in any of the brain regions examined. Although TDP-43 functions may be affected, TDP-43 does not critically regulate expression or splicing of tau in Alzheimer's disease suggesting that TDP-43 contributes to Alzheimer's disease through mechanisms independent of tau.

SUBMITTER: Niblock M 

PROVIDER: S-EPMC4706155 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Lack of association between TDP-43 pathology and tau mis-splicing in Alzheimer's disease.

Niblock Michael M   Hortobágyi Tibor T   Troakes Claire C   Al-Sarraj Safa S   Spickett Carl C   Jones Rebecca R   Shaw Christopher E CE   Gallo Jean-Marc JM  

Neurobiology of aging 20151009


A proportion of Alzheimer's disease cases displays inclusions of the RNA-binding protein, TDP-43. Considering the pathogenic role of tau mis-splicing, we compared tau isoform expression between Alzheimer's disease cases with or without TDP-43 inclusions. The average ratio of tau isoforms containing or lacking exon 10 (4R/3R ratio) or the total level of tau mRNA was not significantly different between cases with or without TDP-43 pathology in any of the brain regions examined. Although TDP-43 fun  ...[more]

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