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• W2981318111 abstract "Identification of different phenotypes of microglia in Alzheimer's disease (AD) will aid in understanding of inflammatory processes. CD105 is a co-receptor that modulates transforming growth factor beta (TGFβ) signaling. CD105 has long been used as a marker for endothelial cells but was originally identified as a marker of activated macrophages. In this study, we characterized an antibody to CD105 that recognizes a variant of CD105 present on subtypes of activated microglia not endothelial cells. This study employed fixed human brain tissue sections and protein extracts of middle temporal gyrus (MTG) from a large series of low plaque (LP), high plaque (HP) non-demented (ND) and AD cases. For comparison, sections from hippocampus, cerebellum and substantia nigra were used. Cellular localization of variant CD105 using a mouse monoclonal antibody (R&D Systems, MAB1097) was identified by enzyme and laser confocal immunohistochemistry. Colocalization was identified with other antibodies to CD105, and antibodies to amyloid beta (Aβ), phosphorylated tau (pTAU), microglial markers lBA-1, CD45, and HLA-DR. The specificity of this CD105 antibody was characterized by peptide absorption and by western blots. Using this CD105 antibody, subtypes of microglia were stained in AD brain sections which represented only a percentage of HLA-DR or IBA-1 positive microglia. Limited numbers of cells stained positive in sections from ND cases. This antibody identified cells with various activated morphologies with most being associated with AD plaques and tangles, while microglia with unactivated morphologies were negative. In comparison with other CD105 antibodies, this antibody did not identify blood vessels. Absorption of antibody with immunizing protein abolished immunostaining of microglia. By western blot, antibody MAB1097 identified a polypeptide of 70 kDa in protein extracts from brain, activated macrophages and endothelial cells, but not the higher molecular weight forms of CD105 recognized by other antibodies. This suggested that MAB1097 was identifying unglycosylated and not glycosylated CD105. Increased CD105 expression by microglia could reduce the anti-inflammatory effects of TGFβ making them more activated. This would be consistent with the increased numbers in diseased tissues. Additional studies are required to further characterize the features of this form of CD105." @default.
• W2981318111 created "2019-10-25" @default.
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• W2981318111 date "2019-07-01" @default.
• W2981318111 modified "2023-09-28" @default.
• W2981318111 title "P4-510: IMMUNOPHENOTYPING OF MICROGLIA: CHARACTERIZATION OF A VARIANT OF CD105 AS A MARKER OF ACTIVATED MICROGLIA IN ALZHEIMER'S DISEASE AND AGED BRAINS" @default.
• W2981318111 doi "https://doi.org/10.1016/j.jalz.2019.08.056" @default.
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