Inhomogeneous Distribution of Iba-1 Characterizes Microglial Pathology in Alzheimer's Disease

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Microglial dystrophy has recently been described as a morphological phenotype of microglia that differs from resting and activated states by spheroid formation and cytorrhexis. In thick sections immunolabeled for HLA-DR or Iba-1 dystrophic microglial processes lose their typical, homogeneous staining pattern and appear to be fragmented or clustered. In this study, we performed double immunofluorescence and electron microscopy to determine if this labeling pattern indeed reflects complete separation of microglial processes from the soma. Using Iba-1/CD68 and Iba-1/MHC class II, as microglial markers, we observed that isolated Iba-1 fragments were still connected to each other by segments of the microglial process immune positive for CD68 or MHC class II. Ultrathin serial sections of two Iba-1 fragments which appeared to be disconnected from each other at the light microscopical level revealed a still existing “bridge” with a diameter of around 0.182 μm. Therefore, microglial dystrophy may reflect alterations of the cytoskeleton ultimately leading to slow cytorrhexis. GLIA 2016;64:1562–1572Main PointsWe show that what appears to be fragmented Iba-1+ microglial processes exhibits MHC-II or CD68-positive ‘bridges’ in-between.Thus, inhomogeneous intracellular distribution rather than cytorrhexis characterizes microglial ageing.

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