Astrocytic tau pathology positively correlates with neurofibrillary tangle density in progressive supranuclear palsy

Tufted astrocytes (TAs) are considered reliable, specific markers for the neuropathologic diagnosis of progressive supranuclear palsy (PSP). It is known that neurofibrillary tangles (NFTs) may relate directly to neurodegeneration, but the role of glial tau pathology is not well determined. To examine the hypothesis that TAs are as pathogenic as NFTs and that both might have a common accumulation, we evaluated the topographic relationship between TAs and NFTs in 12 cases of PSP. The sections of 13 different parts of the brain were stained using the Gallyas-Braak method, and TAs and NFTs were counted and compared statistically. The number of TAs significantly correlated with that of NFTs in the central gray matter, pontine nuclei, and tegmentum, which are responsible for the main symptoms in PSP. In the examined allocortex, however, NFTs were abundant without accompanying TAs. Staining with the specific antibody for 4-repeat tau (RD4) and 3-repeat tau (RD3) was performed to clarify this discrepancy from the standpoint of tau isoforms. NFTs in the entorhinal cortex were stained with both RD3 and RD4, but NFTs in the premotor cortex were stained with only RD4. The nature of NFTs in the allocortical area was different from that of the isocortex in PSP. TAs in the isocortex may share the same pathologic cascade with NFTs stained only by RD4. These results suggest that TAs are part of the same pathologic process as NFTs in PSP.