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 journalArticle

30 Citations (Scopus)

Abstract

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
Volume32
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

Fingerprint

Neurodegenerative Diseases
Parkinson Disease
Mutation
Amyotrophic Lateral Sclerosis
Exons
Genes
Alzheimer Disease

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Ticozzi, N., LeClerc, A. L., Van Blitterswijk, M., Keagle, P., McKenna-Yasek, D. M., Sapp, P. C., ... Landers, J. E. (2011). Mutational analysis of TARDBP in neurodegenerative diseases. Neurobiology of Aging, 32(11), 2096-2099. https://doi.org/10.1016/j.neurobiolaging.2009.11.018

Mutational analysis of TARDBP in neurodegenerative diseases. / Ticozzi, Nicola; LeClerc, Ashley Lyn; Van Blitterswijk, Marka; Keagle, Pamela; McKenna-Yasek, Diane M.; Sapp, Peter C.; Silani, Vincenzo; Wills, Anne Marie; Brown, Robert H.; Landers, John E.

In: Neurobiology of Aging, Vol. 32, No. 11, 11.2011, p. 2096-2099.

Research output: Contribution to journalArticle

Ticozzi, N, LeClerc, AL, Van Blitterswijk, M, Keagle, P, McKenna-Yasek, DM, Sapp, PC, Silani, V, Wills, AM, Brown, RH & Landers, JE 2011, 'Mutational analysis of TARDBP in neurodegenerative diseases', Neurobiology of Aging, vol. 32, no. 11, pp. 2096-2099. https://doi.org/10.1016/j.neurobiolaging.2009.11.018
Ticozzi, Nicola ; LeClerc, Ashley Lyn ; Van Blitterswijk, Marka ; Keagle, Pamela ; McKenna-Yasek, Diane M. ; Sapp, Peter C. ; Silani, Vincenzo ; Wills, Anne Marie ; Brown, Robert H. ; Landers, John E. / Mutational analysis of TARDBP in neurodegenerative diseases. In: Neurobiology of Aging. 2011 ; Vol. 32, No. 11. pp. 2096-2099.
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