Lack of association between TDP-43 pathology and tau mis-splicing in Alzheimer's disease.
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.
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Michael
M
Niblock
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Tibor
T
Hortobágyi
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; London Neurodegenerative Disease Brain Bank, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Claire
C
Troakes
London Neurodegenerative Disease Brain Bank, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Safa
S
Al-Sarraj
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Carl
C
Spickett
Division of Psychiatry, Faculty of Brain Sciences, University College London, London, United Kingdom.
Rebecca
R
Jones
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Christopher E
CE
Shaw
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. Electronic address: jean-marc.gallo@kcl.ac.uk.
Jean-Marc
JM
Gallo
D017398:Alternative Splicing; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D019154:Protein Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; C054369:MAPT protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; C000598624:TARDBP protein, human; D016875:tau Proteins
Alzheimer's disease; Splicing; TDP-43; Tau; Tauopathy