Non-Alzheimer-type
dementias occur in association with a variety of pathological conditions that include a group of diseases characterized by
atrophy of the frontal and temporal lobes.
Frontotemporal dementia (FTD) is a clinical entity that comprises at least two distinct diseases:
Pick's disease with Pick bodies and
frontotemporal lobar degeneration with ubiquitin-positive inclusions (
FTLD-U). The vast majority of
FTLD-U is now referred to as
FTLD-TDP, following the recent discovery of TAR
DNA-binding protein of 43 kDa (TDP-43) as the major constituent of the
ubiquitin-positive inclusions.
FTLD-TDP, but not
Pick's disease with Pick bodies, is often associated with
motor neuron disease (MND). MND is a group of diseases in which the central nervous system lesions were long believed to be confined to the motor neuron system. In other words, MND was not considered to be associated with other neurological symptoms such as
dementia. Nevertheless, more than 200 FTD cases associated with clinical MND have been reported in Japan since 1964. Neuropathologically, MND in such FTD cases was essentially similar to MND in cases without
dementia. The combination of FTD and MND was so characteristic that we considered these cases comprise a unique clinicopathological subgroup of FTD. FTD with MND and the classical MND without
dementia share the occurrence of ubiquitinated TDP-43-positive inclusions, a finding that could be a key to unlock the pathological backgrounds of both diseases.