title: Bcl-xl-specific antibody labels activated microglia associated with Alzheimer's disease and other pathological states.
abstract: This report describes the production of a monoclonal antibody raised against Bcl-xl, and includes an initial study of bcl-xl expression in neuropathology including Alzheimer's disease (AD). Bcl-xl is a potent apoptotic inhibitor and is known to be the predominant Bcl-x isoform in brain. To examine the expression of bcl-xl in aged brain and neurodegenerative disease, we raised a Bcl-xl-specific monoclonal antibody. In aged human brain, the highest bcl-xl expression was observed in cerebellum. By immunohistochemistry, significant bcl-xl expression was detected in reactive microglia of patients with AD and other neurological diseases such as progressive supranuclear palsy. Bcl-xl-positive microglia frequently colocalized with beta-amyloid plaques in AD and with activated astrocytes in non-AD and AD brains, suggesting a general role for Bcl-xl in regions of pathology. High levels of Bcl-xl protein might render microglia more resistant to cytotoxic environments such as areas of neurodegeneration and astrogliosis.
authors.affiliation: Institute for Dementia Research, Bayer Corporation, West Haven, Connecticut 06516, USA.
authors.forename: B
authors.initials: B
authors.lastname: Drache
authors.forename: G E
authors.initials: GE
authors.lastname: Diehl
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: L S
authors.initials: LS
authors.lastname: Perlmutter
authors.forename: G
authors.initials: G
authors.lastname: König
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured / Q000737:chemistry; D005911:Gliosis / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology; D051379:Mice; D017628:Microglia / Q000737:chemistry* / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000276:immunology; D051020:bcl-X Protein
chemical_list: D000911:Antibodies, Monoclonal; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; C494813:Bcl2l1 protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051020:bcl-X Protein