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.

• Authors: Michael Niblock, Tibor Hortobágyi, Claire Troakes, Safa Al-Sarraj, Carl Spickett, Rebecca Jones, Christopher E Shaw, Jean-Marc Gallo
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 37 Pg. 45-46 (Jan 2016) ISSN: 1558-1497 [Electronic] United States
• PMID: 26507309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• DNA-Binding Proteins
• MAPT protein, human
• Protein Isoforms
• RNA, Messenger
• TARDBP protein, human
• tau Proteins

Topics

• Alternative Splicing
• Alzheimer Disease (genetics, metabolism, pathology)
• Brain (metabolism, pathology)
• DNA-Binding Proteins (genetics, metabolism)
• Exons
• Gene Expression
• Genetic Association Studies
• Humans
• Protein Isoforms (genetics, metabolism)
• Protein Splicing (genetics)
• RNA, Messenger (metabolism)
• tau Proteins (genetics, metabolism)