Perivascular orientation of astrocytic plaques and tuft-shaped astrocytes

Astrocytic plaques (APs) and tuft-shaped astrocytes (TAs) are frequently found in the brains of patients with corticobasal degeneration or progressive supranuclear palsy and are considered histopathological markers of these clinicopathological entities. Possible involvement of blood vessels in these lesions, occasionally found in routine histological examination, was estimated by observing thick sections (50–100 μm). The relative distance between the center of each AP/TA to the nearest blood vessel was lesser than that between the nearest blood vessel and control random reference points, and this finding confirmed that APs/TAs are formed in close proximity to blood vessels. Furthermore, three-dimensional reconstruction of sections double-immunolabeled for phosphorylated tau (AT8) and blood vessels (von Willebrand factor) showed the smaller diameter of TAs (mean ± SD, 31.3 ± 5.2 μm; n = 15) and closer contact of their AT8-positive processes to blood vessels, representing proximal accumulation of phosphorylated tau in TAs. This is in contrast with larger APs (88.5 ± 15.2 μm, n = 63), in which AT8-positive processes rarely have vascular contact. Even though the endfeet of astrocytes come into close contact with blood vessels, tau deposition, observed in both TAs and APs, was always oriented around the blood vessel, implying that these apparently distinct lesions (APs/TAs) share a common mechanism for tau deposition that is oriented around the blood vessel.

► Three-dimensional reconstruction clarified perivascular orientation for TAs and APs.
► This similarity suggests a shared pathogenesis for these two apparently distinct cytopathologies.
► These similarities and differences may provide more reliable framework to understand PSP and CBD.