Fig. 4

Common neuropathological features of the 3 cases of HDLS studied here. Spheroids were abundant (a) primarily in the deeper white matter without affecting the short association fibers; b spheroids had a heterogeneous distribution as is evident by comparing the left and right side of the image; c focal very dense clusters of spheroids were seen (Case #3, orbital frontal cortex). d Microglia were not diffusely distributed and were of two distinct populations. Many microglia had morphologies indicative of (e) activated phagocytic macrophages that were CD68 positive and Iba1 negative with unusually ramified morphologies (f) while others were Iba1 positive microglia with more simple morphologies (Case #2, anterior corpus callosum). Occasionally, additional pathologies included (g) patches of calcifications (Case #2, blue-black splotchy areas in the anterior corpus callosum) and (h) irregular neuronal accumulations of pathological tau (Case #3, anterior cingulate). i Spheroids could also be visualized by tau, ubiquitin and α-synuclein antibodies (not shown here as well as by anti-neurofilament antibodies (shown here for Case #1 in the angular gyrus). Antibodies and stains used: (a-c) 22c11, (d-e) CD68, (f) Iba1, (g) H&E, (h) PHF1, (i) RMO24.9