Amyotrophic lateral sclerosis with dementia (ALSD), corresponding to the motor neuron disease type of frontotemporal dementia, is neuropathologically characterized by depletion of the motor neurons, degeneration of the extra-motor cerebral cortices and formation of ubiquitin-immunoreactive (not argyrophilic, tau-negative, alpha-synuclein-negative) intraneuronal inclusions. Recently, immunoreactivity for ubiquitin-binding protein p62 has been reported in several ubiquitin-containing intraneuronal or intraglial inclusions (e.g. neurofibrillary tangles, Pick bodies, Lewy bodies, glial cytoplasmic inclusions) in various neurodegenerative diseases. We examined p62 immunoreactivity in ubiquitin-immunoreactive intraneuronal inclusions in five ALSD cases with a broad clinicopathological spectrum. p62 immunoreactivity in ubiquitin-immunoreactive intraneuronal inclusions was seen in all cases. The mean proportion of p62-immunoreactive inclusions to the total number of ubiquitin-immunoreactive inclusions (p62/Ub ratio) in the dentate gyrus was 27.5 +/- 16.6% (range 6.3-47.3%). There was no correlation between p62/Ub ratio and the severity of dementia, duration of illness or neuropathological severity. Although the main constituent of these inclusions is unknown, our study suggests that p62 contributes to the formation of the inclusions via the same mechanism as in other previously reported neurodegenerative diseases. Since p62 is believed to have a neuroprotective role, the formation of these inclusions may represent a non-harmful, rather protective effect against the neuronal degeneration in ALSD.