Cortical ubiquitin-positive inclusions in frontotemporal dementia without motor neuron disease: a quantitative immunocytochemical study.

Ubiquitin-positive tau-negative inclusions were initially described in the rare form of frontotemporal dementia (FTD) associated with motor neuron disease. However, recent studies have indicated that these inclusions are also present in typical FTD, which is usually characterized by nonspecific histological changes. To examine the contribution of these inclusions to neuronal loss and to explore their relationship with disease duration, we performed a quantitative immunocytochemical analysis of 38 typical FTD cases. Relationships between neuron and ubiquitin inclusion densities as well as between duration of illness and neuropathological parameters was studied using linear regression in both univariate and multivariate models. Ubiquitin-positive tau-negative intracytoplasmic inclusions were present in 65.8% of cases in the dentate gyrus, 57.9% in temporal cortex and 31.6% in frontal cortex. The highest densities of ubiquitin-positive inclusions were consistently observed in the dentate gyrus, followed by the temporal and frontal cortex. There was no statistically significant relationship between neuron and ubiquitin-positive inclusion densities in any of the areas studied. In contrast, ubiquitin-positive inclusion densities in the dentate gyrus were negatively related to the duration of illness. Our data suggest that the development of ubiquitin-related pathology is the rule and not the exception in typical FTD, yet is not causally related to neuronal loss. They also reveal that the development of ubiquitin-positive inclusion densities in the dentate gyrus may be associated with a more aggressive form of the disease.