Argyrophilic grain disease (AGD) is a progressive disorder producing dementia in elderly individuals characterized by the presence of numerous AGs in the limbic system. However, the occurrence of AGs has been reported in other neurodegenerative conditions including Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration, all of which show tau-positive cytoskeletal abnormalities. We examined the brains of 26 patients with multiple system atrophy (MSA), a neurodegenerative disorder fundamentally lacking tau pathology, histologically and immunocytochemically. Numerous AGs were found in the limbic system in 5 patients, of whom two had shown mild dementia. Immunocytochemically, these AGs were labeled with antibodies against phosphorylation-dependent and -independent tau protein, but not alpha-synuclein, whereas oligodendroglial cytoplasmic inclusions found exclusively in MSA were immunoreactive for alpha-synuclein and, less consistently, for phosphorylation-independent tau but not for phosphorylation-dependent tau protein. Furthermore, many phosphorylation-dependent tau-positive neurons and significant numbers of ballooned neurons (BNs) were found in the limbic system in all of the 5 patients with AGs. These findings suggest that AGs can occur with relatively high frequency in the limbic system of MSA patients, and that as in AGD, they may be accompanied by tau-positive neurons and BNs.
Aged Brain