TDP-43 variants of frontotemporal lobar degeneration

Eileen H. Bigio*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


It has been only 5 years since the identification of TDP-43 as the major protein component of the ubiquitinated inclusions in FTLD-U. At that time, there were approximately a dozen papers about TDP-43; today, a "TDP-43" search reveals almost 600 papers. It is now clear that the majority of FTLD cases containing tau- and alpha-synuclein-negative, ubiquitin-positive inclusions (FTLD-U) are FTLD-TDP. The spectrum of TDP-43 proteinopathies includes FTLD-TDP with or without ALS, with or without mutations in GRN, VCP, or TARDBP, with or without chromosome 9p linkage, and sporadic and non-SOD1 familial ALS with or without FTLD-TDP. There are four sub-types of FTLD-TDP, and these correlate with specific clinical and genetic profiles. Sub-types are determined by the presence, predominance, and distribution of the various TDP-43 immunopositive insoluble aggregates-neuronal cytoplasmic inclusions, neuronal intranuclear inclusions, and dystrophic neurites. In this paper, FTLD-TDP pathologic sub-types will be described, and examples of each sub-type will be shown, and implications for future research will be discussed.

Original languageEnglish (US)
Pages (from-to)390-401
Number of pages12
JournalJournal of Molecular Neuroscience
Issue number3
StatePublished - Nov 2011


  • ALS
  • Amyotrophic lateral sclerosis
  • FTD
  • FTLD-U
  • Frontotemporal dementia
  • GRN
  • Progranulin
  • TAR-DNA binding protein-43
  • TDP-43

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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