A study of dementia with argyrophilic grains. Possible cytoskeletal abnormality in dendrospinal portion of neurons and oligodendroglia

Abstract

Two mildly demented patients with emotional disorder presented massive cortical argyrophilic grains (ArG) in the limbic area and coiled bodies mainly in the white matter. Immunohistochemically, the ArG consisted of partially ubiquitinated full-length phosphorylated tau. A modified Gallyas-Braak method, used after potassium permanganate and oxalic acid pretreatment, revealed many filiform, knobby or pleomorphic spine-like appendages on the ArG. Double immunohistochemical staining using anti-tau with either anti-microtubule-associated protein 2 or anti-neurofilament 200K revealed that ArG were intimately associated with dendrites rather than with axons. Electron microscopic studies with tau immunohistochemistry and the Gallyas-Braak method revealed that the ArG were composed of bundles of smooth tubules of 25-nm diameter. The coiled body-bearing cells had the morphological characteristic of oligodendroglia. These results indicate that the presence of ArG is a cytoskeletal abnormality affecting predominantly the dendrospinal portions of neurons. A survey of diseases with cytoskeletal disorders revealed that a small number of similar argyrophilic granular structures are sometimes observed in progressive supranuclear palsy, Pick's disease with Pick bodies and corticobasal degeneration. Dementia with ArG is thought to be a unique cytoskeletal abnormality associated predominantly with the dendrospinal portions of neurons and oligodendroglia.