Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 66, Issue 3, Pages 177-183Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.jnen.0000248554.45456.58
Keywords
frontotemporal dementia; TDP-43; ubiquitin; white matter lesions
Categories
Funding
- NIA NIH HHS [AG10124, P01 AG019724, AG17586, P01 AG017586] Funding Source: Medline
Ask authors/readers for more resources
TDP-43 was recently identified as the major disease protein in neuronal inclusions in firontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). TDP-43 is not only linked to disease mechanisms in FTLD-U, but it is also the most robust marker for the specific detection of neuronal inclusions in FTLD-U. In this study, we describe additional TDP-43 pathology in the white matter as a characteristic feature in a series of 38 FTLD-U cases including 3 cases with mutations in the progranulin gene. White matter pathology was most abundant in frontal and temporal lobes, but it was also detectable in brainstent and spinal cord. Based on morphology and double-labeling experiments, white matter cells with TDP-43-positive inclusions most likely represent oligodendrocytes. Biochemically, hyperphosphorylated and truncated TDP43 was detectable in insoluble brain extracts from affected white matter regions in FTLD-U, similar to the biochemical signature observed in FTLD-U gray matter. Taken together, these results expand the spectrum of TDP-43 pathology in FTLD-U, suggesting that white matter pathology might contribute to the neurodegenerative process and clinical symptoms in FTLD-U.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available