Cytoskeletal alterations in the human tuberal hypothalamus related to argyrophilic grain disease.

The tuberal region of the human hypothalamus was examined for cytoskeletal changes related to argyrophilic grain disease (AGD). Hypothalamic sections of eight individuals afflicted with AGD and eight controls were cut serially in the frontal plane at 100 microm. The presence of argyrophilic AGD-related pathology was demonstrated utilizing the modified Gallyas silver iodide technique. Tau-positive cytoskeletal changes were stained by the phosphorylation-dependent antibody AT8. A characteristic pattern of tau-positive cytoskeletal alterations was revealed in the tuberal hypothalamus of AGD cases, while controls were devoid of such changes. The lateral tuberal nucleus was found to be particularly susceptible to AGD, demonstrating numerous tau-positive grains and neuronal cell bodies. Similar alterations were present to a moderate degree in the ventromedial nucleus. A previously unreported, conspicuous accumulation of tau-positive oligodendrocytes (coiled bodies) and interfascicular thread-like fibers was detected in the column of the fornix. Only sparse argyrophilic changes were noted in consecutive silver-stained sections, comprised mainly of accumulations of spindle-shaped grains within the lateral tuberal nucleus. Remarkably, a pronounced expression of AGD-related alterations was seen in the absence of hypothalamic changes related to other tau-positive cytoskeletal disorders, such as Alzheimer's disease. The present findings support the concept that AGD is a distinct neurodegenerative entity afflicting not only cortical but also subcortical predilection sites of the human brain.