The characteristics of perivascular proinflammation in 4-repeat tauopathies
Related Experiment Video
Updated: Oct 30, 2026

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Mu-Hui Fu1,2, Gokhan Uruk1, Rodolfo G Gatto1
1Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Abstract:
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are both neurodegenerative diseases characterized by aggregates composed of 4-repeat (4R) tau protein. They have distinct neuropathological features and classic clinical symptoms; however, the signs and symptoms overlap across the two syndromes. Accumulating evidence suggests that dysregulated immune response is a major contributing factor to neurodegeneration but its role in 4R-tauopathies remains undetermined. The aim is to explore the involvement of neuroinflammation from a vascular perspective in 4R-tauopathies. Autopsies from four controls, three PSP, and three CBD cases were assessed. Samples were obtained from the superior/middle frontal gyrus (S/M-FG) and basal ganglia (BG). Immunofluorescence staining included neuroinflammatory markers: glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), cluster of differentiation 68 (CD68); vascular markers: collagen type IV (ColIV), monocarboxylate transporter-1 (MCT1), and α-smooth muscle actin (αSMA). Maximally projected confocal z-stack images of vasculature were used as a mask to quantify total perivascular GFAP+/Iba1+/CD68+ labeling. GFAP immunoreactivity ratio between MCT1 and αSMA double labeled arteries and veins was quantified to further differentiate venular and arteriolar involvement into proinflammatory activation. Both PSP and CBD had widespread perivascular proinflammatory changes, although greater in CBD. The activated GFAP+ astrocytes and microglia/macrophages in CBD were distributed extensively in S/M-FG and BG, with S/M-FG WM more affected. In PSP, abundant neuroinflammation was found in BG. The involvement of vasculature type was distinct among the two 4R-tauopathies, while CBD showed comparable proinflammatory changes in arterioles and venules, PSP exhibited predominant proinflammation in venules. The regional pattern of perivascular proinflammation differed between PSP and CBD, corresponding to the characteristic affected brain regions. CBD had more severe perivascular proinflammation that involved both arterioles and venules, while venules were more affected in PSP. Perivascular proinflammation may be a critical pathophysiological process in 4R-tauopathies.
Related Concept Videos
Alzheimer Disease ll: Pathophysiology
Encephalitis ll: Pathophysiology
Chronic Inflammation: Introduction
Parkinson Disease ll: Pathophysiology
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Dementia l: Introduction

