title: Glial fibrillary acidic protein isoform expression in plaque related astrogliosis in Alzheimer's disease.
abstract: In Alzheimer's disease (AD), amyloid plaques are surrounded by reactive astrocytes with an increased expression of intermediate filaments including glial fibrillary acidic protein (GFAP). Different GFAP isoforms have been identified that are differentially expressed by specific subpopulations of astrocytes and that impose different properties to the intermediate filament network. We studied transcript levels and protein expression patterns of all known GFAP isoforms in human hippocampal AD tissue at different stages of the disease. Ten different transcripts for GFAP isoforms were detected at different abundancies. Transcript levels of most isoforms increased with AD progression. GFAPδ-immunopositive astrocytes were observed in subgranular zone, hilus, and stratum-lacunosum-moleculare. GFAPδ-positive cells also stained for GFAPα. In AD donors, astrocytes near plaques displayed increased staining of both GFAPα and GFAPδ. The reading-frame-shifted isoform, GFAP(+1), staining was confined to a subset of astrocytes with long processes, and their number increased in the course of AD. In conclusion, the various GFAP isoforms show differential transcript levels and are upregulated in a concerted manner in AD. The GFAP(+1) isoform defines a unique subset of astrocytes, with numbers increasing with AD progression. These data indicate the need for future exploration of underlying mechanisms concerning the functions of GFAPδ and GFAP(+1) isoforms in astrocytes and their possible role in AD pathology.
authors.affiliation: Netherlands Institute for Neuroscience-an Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Department of Astrocyte Bology and Neurodegeneration, Amsterdam, the Netherlands. Electronic address: w.kamphuis@nin.knaw.nl.
authors.forename: Willem
authors.initials: W
authors.lastname: Kamphuis
authors.forename: Jinte
authors.initials: J
authors.lastname: Middeldorp
authors.forename: Lieneke
authors.initials: L
authors.lastname: Kooijman
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Sluijs
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: Kooi
authors.forename: Martina
authors.initials: M
authors.lastname: Moeton
authors.forename: Michel
authors.initials: M
authors.lastname: Freriks
authors.forename: Mark R
authors.initials: MR
authors.lastname: Mizee
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D018450:Disease Progression; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D058225:Plaque, Amyloid / Q000378:metabolism*; D020033:Protein Isoforms; D012720:Severity of Illness Index; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D005904:Glial Fibrillary Acidic Protein; D020033:Protein Isoforms
keywords: Alzheimer's disease; Astrocytes; GFAP; Glial fibrillary acidic protein; Gliosis; Hippocampus; Intermediate filaments; Isoforms; Nestin; Plaques; Synemin; Vimentin