Astrocytes expressing hyperphosphorylated tau protein without glial fibrillary tangles in argyrophilic grain disease

Argyrophilic grain disease (AgD), a frequent type of late onset dementia, i s characterized by the occurrence of Gallyas-stained neuropil grains in the hippocampus, entorhinal cortex, amygdala and hypothalamus. High numbers of neurons containing hyperphosphorylated tau protein, but devoid of tangles, are encountered in areas rich in argyrophilic grains (ArGs). A third type of change consists of slender argyrophilic and tau-immunoreactive cytoplasm ic inclusions in white matter oligodendrocytes, the coiled bodies. We now e xtend earlier studies on glial pathology in Ago (20 cases) and compare the results with glial changes in old age (10 cases) and Alzheimer's disease (A D; 7 cases). Numerous non-argyrophilic, non-neuronal tau-positive stellate cells in the amygdala and anterior entorhinal cortex were consistently foun d in all of the 20 Ago cases but not in AD cases. Double-labelling experime nts performed on paraffin sections with phosphorylation-dependent anti-tau antibody AT8, anti-glial fibrillary acidic protein and anti-CD44, revealed coexpression of these markers in stellate cells. The high expression of CD4 4 indicate that they probably correspond to reactive astrocytes. Unlike ast rocytic plaques in corticobasal degeneration (CBD), where AT8 reactivity is accumulating in distal astrocytic processes, tau reactivity in Ago was fou nd in all astrocytic cell compartments. The absence of glial fibrillary tan gles further distinguished tau-labelled astrocytes in Ago from astrocytic p laques in CUD and tufted astrocytes in progressive supranuclear palsy (PSP) . In contrast to AD and aged non-demented control cases tau-positive non-ar gyrophilic astrocytes represent a consistent finding in anterior limbic str uctures in Ago. Our findings point to a more widespread pathology of the gl ial cell population in Ago than previously supposed, and will be of further help in differentiating Ago from other neurodegenerative disorders, includ ing AD, PSP, CBD and Pick's disease.