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.
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Authors | Kimmo 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 |
Journal | Journal of neuropathology and experimental neurology
(J Neuropathol Exp Neurol)
Vol. 67
Issue 4
Pg. 271-9
(Apr 2008)
ISSN: 0022-3069 [Print] England |
PMID | 18379440
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA-Binding Proteins
- Ubiquitin
- tau Proteins
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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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