TAR-DNA-binding protein 43 (TDP-43) has been identified as a major component protein
of ubiquitin-positive inclusions in brains from patients with frontotemporal lobar
degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis.
To obtain the precise prevalence of TDP-43 pathology in neurodegenerative disorders,
we examined brains from patients with tauopathies and synucleinopathies as well as
FTLD-U using immunohistochemical analysis. Consequently, TDP-43-positive inclusions
within neurons and oligodendroglia were found in brains from patients with Alzheimer's
disease (AD) and dementia with Lewy bodies (DLB) in addition to FTLD-U, but not with
Parkinson's disease, Pick's disease, progressive supranuclear palsy, corticobasal
degeneration or FTDP-17. The amygdala and hippocampus that were vulnerable to tau
or alpha-synuclein pathology demonstrated more severe TDP-43 pathology in AD and DLB
cases than in FTLD-U cases. In contrast, in the frontal cortex and basal ganglia that
were vulnerable to TDP-43 pathology in FTLD-U, TDP-43 pathology was not observed in
AD and DLB cases. Thus, the neuroanatomical distribution of TDP-43 pathology in AD
and DLB cases was obviously different from that in FTLD-U cases. Furthermore, a subset
of TDP-43-positive inclusions co-existed with neurofibrillary tangles (NFTs) or Lewy
bodies (LBs) in the same neurons. Upon double-immunofluorescent labeling analysis,
TDP-43 was hardly superimposed with tau, while TDP-43 was partially superimposed with
alpha-synuclein, suggesting that neither NFTs nor LBs themselves show TDP-43 immunoreactivity
and that TDP-43 pathology found in this study may be related in some way to AD and
LB pathology. This study will provide a more in-depth understanding of the various
pathogenic pathways leading to neurodegenerative disorders.