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The pathology and nosology of primary progressive aphasia

We present three cases of primary progressive aphasia (PPA) with Pick-variant pathology to support a hypothesis of an underlying nosologic relatedness. Neuropathologic examination demonstrated focal brain atrophy with corresponding neuronal loss and gliosis, accompanied by superficial spongiosis. Specific histologic findings were ballooned neurons (Pick cells) in the atrophic areas, and in two of the cases, Pick bodies. They were immunoreactive for tau. In contrast to classic Pick's disease, there were no Pick bodies in the hippocampus. The intense neurofilament immunoreactivity of the perikarya of the ballooned neurons greatly facilitated their recognition. Based on our cases and a critical review of the literature, we hypothesize that the common underlying pathology of PPA is a variant of Pick's disease. Furthermore, we propose the concept of “Pick complex” to include other neurodegenerative diseases characterized by focal cortical degeneration, such as PPA, frontal lobe dementia, ALS with PPA, and corticonigral and corticobasal ganglionic degenerations.