Details

Autor(en) / Beteiligte

• Hatanpaa, Kimmo J
• Bigio, Eileen H
• Cairns, Nigel J
• Womack, Kyle B
• Weintraub, Sandra
• Morris, John C
• Foong, Chan
• Xiao, Guanghua
• Hladik, Christa
• Mantanona, Tina Y
• White, Charles L

Titel

TAR DNA-Binding Protein 43 Immunohistochemistry Reveals Extensive Neuritic Pathology in FTLD-U: A Midwest-Southwest Consortium for FTLD Study

Ist Teil von

• Journal of neuropathology and experimental neurology, 2008-04, Vol.67 (4), p.271-279

Ort / Verlag

Hagerstown, MD: American Association of Neuropathologists, Inc

Erscheinungsjahr

2008

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.