Cellular tau pathology and immunohistochemical study of tau isoforms in sporadic tauopathies

Abstract

Pathological inclusions in neurons and glial cells containing fibrillary aggregates of abnormally hyperphosphorylated tau protein are characteristic features in sporadic tauopathies. In the first part of this paper we outline the morphological features of some major sporadic tauopathies. In the second part, to better define the tau isoform composition, we report on the immunohistochemistry of tau isoforms in autopsied brains, including two cases with AD, two with diffuse neurofibrillary tangles with calcification, four with Pick's disease with Pick bodies (PiD), seven with progressive supranuclear palsy (PSP), six with corticobasal degeneration (CBD) and seven cases with argyrophilic grain disease. We used two monoclonal antibodies, RD3 and RD4, and a polyclonal antibody for exon 10 that effectively distinguish between three-repeat (3R) tau and four-repeat (4R) tau. Neuronal neurofibrillary tangles (NFT) in AD and diffuse neurofibrillary tangles with calcification contained both 3R-tau and 4R-tau. The Pick bodies were immunopositive for 3R-tau in two cases; however, in two other cases they were mainly immunopositive for 4R-tau. Thus, Pick bodies demonstrated heterogeneity. 3R-tau PiD contained 3R-tau glial inclusions, and 4R-tau PiD contained mainly 4R-tau glial inclusions. Glial inclusions were more abundant in 4R-tau PiD cases. In progressive supranuclear palsy and CBD, both neuronal and glial tau accumulation forming NFF, pretangles, tuft-shaped astrocytes, astrocytic plaques, coiled bodies and threads demonstrated 4R-tau in the cerebral cortices, although in the basal ganglia and brainstem neuronal and glial inclusions were occasionally immunopositive for 3R-tau in addition to 4R-tau. Argyrophilic grains (AG) were immunopositive for 4R-tau, although pretangles were weakly stained for 4R-tau. Thus the immunoreactivity for 4R-tau was different between AG and pretangles. Therefore, the isoform composition on immunohistochemical study showed heterogeneity in PiD, and was not uniform in the basal ganglia and brain stem in PSP and CBD. It is suggested that the isoform composition of sporadic tauopathies may have a spectrum in individual cases, and cellular isoform composition may differ in various brain regions.