Immunohistochemical and ultrastructural characterization of neuritic clusters around ghost tangles in the hippocampal formation in progressive supranuclear palsy brains

We performed a detailed study of swollen neurite aggregation surrounding ex tracellular neurofibrillary tangles (ghost tangles, GTs) in brains of patie nts with progressive supranuclear palsy (PSP) by immunohistochemistry and e lectron microscopy (EM). The complex structures, designated as tangle-assoc iated neuritic clusters (TANCs), were found in the hippocampus and parahipp ocampal cortex in all five PSP brains examined. TANCs measured from 20 to 4 0 mu m across; twice as large as nearby neurons. Each neurite was globular or fusiform in shape, measured up to 10 mu m in diameter, and was found bet ween loosened fascicles of GTs or along their outer rims. There were severa l subsets of neurites that were argyrophilic or immunoreactive against anti bodies to either phosphorylated tau protein, phosphorylated neurofilaments, ubiquitin, or synaptophysin. On EM, TANCs consisted of numerous axon termi nals of varying size, which were filled with flocculate dense bodies, vesic ular profiles, and synaptic vesicles, as well as normal-looking and degener ating cell organelles. Some axons had 13- to 15-nm-thick straight tubules t hat showed tau immunoreactivity; however, there was little neurofilament ac cumulation. Most of the swollen axon terminals conformed to the ultrastruct ural features of either reactive or degenerating terminals. The neurites id entified by immunohistochemistry only represented a minority of the swollen axons visualized by EM. Tubules of GTs were dispersed in the extracellular space, but no amyloid fibrils were found. TANCs may constitute a distincti ve form of neuronal degeneration in PSP cortices. We hypothesize that axon terminal accumulation may occur in response to GT-formation.