Argyrophilic thorny astrocyte clusters in association with Alzheimer's disease pathology in possible primary progressive aphasia

Although most cases of primary progressive aphasia (PPA) have one of the varieties of frontotemporal lobar degeneration (FTLD) as their pathological substrate, a subset shows Alzheimer's disease (AD) pathology. We report that all eight cases in our clinic diagnosed as possible PPA, on account of the presence of episodic memory difficulties in addition to severe language impairment at the onset of disease, showed AD pathology. Neither focal accentuation of AD pathology nor vascular lesions in language-related areas was observed. Seven of these eight patients showed large argyrophilic thorny astrocyte clusters (ATAC) in the fronto-temporo-parietal cortex and subcortical white matter. The intensely tau immunoreactive astrocytes in ATAC were morphologically similar to the perivascular, subpial, and subependymal astrocytes in elderly brains, but ATAC differ from the latter by the cortical and subcortical location, widespread distribution outside the medial temporal lobe, and intense argyrophilia. The location of ATAC was related to neither local variations in the load of AD pathology, nor the myelin density of white matter. ATAC were not seen in a comparison group of six cases of AD without a prominent aphasia syndrome. Because of the similarity of astrocytes in ATAC to those seen independently of AD pathology in several subtypes of FTLD and two reported cases of PPA we hypothesize that they are a marker of a pathological process concurrent with AD, and related to the focality of the clinical presentation.