THE NEUROPATHOLOGY OF CHROMOSOME 17-LINKED DEMENTIA

We recently described a family with chromosome 17-linked dementia, cha racterized clinically by disinhibition-dementia-parkinsonism-amyotroph y complex. We report now the neuropathology of 6 affected family membe rs. This included semiquantitative scoring of neuronal loss, gliosis, and spongiosis and immunocytochemical and ultrastructural characteriza tion of neuronal and glial inclusions. The changes consisted of circum scribed neuronal loss, gliosis, and spongiosis of limbic neocortical a reas and frontal, temporal, and occipital association areas. Similar c hanges were present in subcortical nuclei, most severe in the substant ia nigra, but also involved the ventral striatum and amygdala. The hip pocampus was spared except for degeneration of the afferent perforant tract, secondary to entorhinal nerve cell loss, Argyrophilic neuronal inclusions, with a characteristic immunocytochemical profile, were fou nd in brainstem nuclei, hypothalamus, and basal ganglia. Ultrastructur ally, in 3 patients these inclusions showed hitherto undescribed abnor mally assembled filaments. Glial cytoplasmic inclusions were widesprea d in white matter structures. Immunocytochemistry failed to demonstrat e the protease-resistant prion protein. The pathology appears to be un ique, involving various cortical and subcortical structures, and is co nsistent with the clinical findings of Kluver-Bucy-like syndrome, park insonism, and frontal lobe dementia. For this entity we suggest the te rm ''chromosome 17-linked dementia.''