Mutational analysis of TARDBP in neurodegenerative diseases

Nicola Ticozzi, Ashley Lyn LeClerc, Marka van Blitterswijk, Pamela Keagle, Diane M. McKenna-Yasek, Peter C. Sapp, Vincenzo Silani, Anne Marie Wills, Robert H. Brown, John E. Landers

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Neurodegenerative diseases are often characterized by the presence of aggregates of misfolded proteins. TDP-43 is a major component of these aggregates in amyotrophic lateral sclerosis (ALS), but has also been observed in Alzheimer's (AD) and Parkinson's Diseases (PD). In addition, mutations in the TARDBP gene, encoding TDP-43, have been found to be a significant cause of familial ALS (FALS). All mutations, except for one, have been found in exon 6. To confirm this observation in ALS and to investigate whether TARDBP may play a role in the pathogenesis of AD and PD, we screened for mutations in exon 6 of the TARDBP gene in three cohorts composed of 376 AD, 463 PD (18% familial PD) and 376 ALS patients (50% FALS). We found mutations in ~7% of FALS and ~0.5% of sporadic ALS (SALS) patients, including two novel mutations, p.N352T and p.G384R. In contrast, we did not find TARDBP mutations in our cohort of AD and PD patients. These results suggest that mutations in TARDBP are not a significant cause of AD and PD.

Original languageEnglish (US)
Pages (from-to)2096-2099
Number of pages4
JournalNeurobiology of aging
Issue number11
StatePublished - Nov 2011


  • AD
  • ALS
  • Genetics
  • PD
  • TDP-43

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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