Ultrastructural localization of TDP-43 in filamentous neuronal inclusions in various neurodegenerative diseases

Wen Lang Lin, Dennis W. Dickson

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Using post-embedding immunogold electron microscopy, TAR DNA-binding protein of 43 kDa (TDP-43) was localized to neuronal cytoplasmic (NCI) and intranuclear (NII) inclusions, as well as unmyelinated neurites, in frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U), amyotrophic lateral sclerosis (ALS), Alzheimer's (AD), Pick's disease (PiD) and Lewy body disease (LBD). The TDP-43 immunoreactive structures were morphologically heterogeneous. The most common was characterized by bundles of 10-20 nm diameter straight filaments with electron dense granular material within NCI, NII and neurites. This type of pathology was found in FTLD-U, ALS and some cases of AD. Less often, inclusions in neuritic processes of FTLD-U and some cases of AD contained 10-17 nm diameter straight filaments without granular material. A final type of TDP-43 immunoreactivity was labeling of filaments and granular material associated with tau filaments in neurofibrillary tangles of AD and Pick bodies of PiD or α-synuclein filaments in Lewy bodies of LBD. The results suggest that TDP-43 is the primary component of the granulofilamentous inclusions in FTLD-U and ALS. Similar inclusions sometimes accompany filamentous aggregates composed of other abnormal proteins in AD, PiD and LBD.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalActa neuropathologica
Volume116
Issue number2
DOIs
StatePublished - Aug 2008

Keywords

  • Alzheimer's disease
  • Amyotrophic lateral sclerosis
  • Frontotemporal lobar degeneration with ubiquitinated inclusions
  • Immunoelectron microscopy
  • Lewy body disease
  • Pick's disease
  • TAR DNA-binding protein of 43 kDa (TDP-43)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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