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TAR DNA-binding protein 43 immunohistochemistry reveals extensive neuritic pathology in FTLD-U: a midwest-southwest consortium for FTLD study.

Abstract
TAR DNA-binding protein 43 (TDP-43) is a major component of the inclusions in frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U). We studied TDP-43 pathology in the hippocampus and frontal cortex of autopsy brains from patients with FTLD-U (n = 68), dementia lacking distinctive histopathology (n = 4), other neurodegenerative diseases (n = 23), and controls (n = 12) using a sensitive immunohistochemistry protocol. Marked enhancement of staining of TDP-43-positive dystrophic neurites (DNs) was obtained, and we observed 2 previously unrecognized pathologic patterns (i.e. frequent long DNs in the CA1 region and frequent dot-like DNs in the neocortical layer 2) in 39% and 15% of the FTLD-U cases, respectively. Frequent long DNs, but not dot-like DNs, were significantly associated with progranulin mutations. Based on this evaluation, 4 FTLD-U cases showed no TDP-43 pathology and were reclassified as "FTLD-U, non-TDP-43 proteinopathy," and 3 cases of dementia lacking distinctive histopathology were reclassified as FTLD-U. Of the cases with other neurodegenerative diseases, 43% showed TDP-43 pathology in the hippocampus, but only 4% showed TDP-43 pathology in the frontal cortex. No TDP-43 pathology was seen in controls. These results indicate that the sensitivity of the TDP-43 immunohistochemistry method affects both the extent and type of abnormalities detected. Moreover, assessment of abnormalities in both the hippocampus and frontal cortex may be diagnostically important in FTLD-U.
AuthorsKimmo J Hatanpaa, Eileen H Bigio, Nigel J Cairns, Kyle B Womack, Sandra Weintraub, John C Morris, Chan Foong, Guanghua Xiao, Christa Hladik, Tina Y Mantanona, Charles L White 3rd
JournalJournal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 67 Issue 4 Pg. 271-9 (Apr 2008) ISSN: 0022-3069 [Print] England
PMID18379440 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA-Binding Proteins
  • Ubiquitin
  • tau Proteins
Topics
  • Aged
  • Autopsy
  • DNA-Binding Proteins (metabolism)
  • Dementia (metabolism, pathology)
  • Female
  • Frontal Lobe (metabolism, pathology)
  • Hippocampus (metabolism, pathology)
  • Humans
  • Male
  • Middle Aged
  • Neurites (metabolism, pathology)
  • Plaque, Amyloid (pathology)
  • Ubiquitin
  • tau Proteins (metabolism)

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