Diffuse form of argyrophilic grain disease: a new variant of four-repeat tauopathy different from limbic argyrophilic grain disease.

Argyrophilic grain disease (AGD) is characterized by the occurrence of argyrophilic grains and coiled bodies in brain tissue, mainly in limbic areas located in the temporal lobe. Recent biochemical data have shown that inclusions in AGD consist of aggregates of pathological microtubule-associated tau protein isoforms of 64/69 kDa. We report here a study on two AGD patients, belonging to a series of demented patients affected by several tauopathies, prospectively followed until death. In both patients, clinical, neuropathological and biochemical investigations clearly demonstrated AGD. Diffuse tau pathology was shown by Gallyas' silver stain, tau immunohistochemistry and tau protein variant biochemical analysis, not only in temporal lobes but also in all cortical and subcortical areas that were assessed. Primary motor, primary sensory, and associative brain cortices were involved, as well as brain stem, but not cerebellum. We suggest that "diffuse" AGD might be a subgroup of AGD, the specific profile of which is different from that of "limbic" AGD.