Immunohistochemical study of microscopic globular bodies of normal human brain

Microscopic globular bodies (MGBs) are brilliantly and homogenously eosinophilic spherical inclusions, 1-10 μm in diameter. They are mainly distributed in the cerebral neocortex and hippocampus in normal individuals ranged in age from first to tenth decade. Ultrastructurally, MGBs are composed of electron-dense granular material and are located in dendrites. However, immunohistochemical profile of MGBs is uncertain. Therefore, we immunohistochemically examined the hippocampus from five control subjects ranged from 25 to 76 years. The marginal portion of MGBs was positive for lysosomal proteases (cathepsins B, D and L), and markers of dendrite (MAP2) and dendritic spine (drebrin). In some cases, MGBs were entirely immunostained with anti-cathepsin D. Among the cathepsins, MGBs were most frequently immunolabeled with anticathepsin D. They were negative for ubiquitin, ubiquitin-proteasome system (p62, NUB1 and EDD1), autophagosome (LC3), cytoskeletal proteins (neurofilament, actin, tubulin and cytokeratin), tau, α-synuclein and TDP-43. These findings suggest that MGBs are sequestered by lysosome- protease system, but not by ubiquitin-proteasome system or autophagosome.