Ultrastructural localization of TDP-43 in filamentous neuronal inclusions in various neurodegenerative diseases.
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 alpha-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.
Lin
Wen-Lang
WL
Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Dickson
Dennis W
DW
D004268:DNA-Binding Proteins / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000648:ultrastructure*; D016253:Microscopy, Immunoelectron; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*
D004268:DNA-Binding Proteins