title: Aggregation of the Inflammatory S100A8 Precedes Aβ Plaque Formation in Transgenic APP Mice: Positive Feedback for S100A8 and Aβ Productions.
abstract: Inflammation plays an important role in Alzheimer's disease (AD) and other neurodegenerative disorders. Although chronic inflammation in later stages of AD is well described, little is known about the inflammatory processes in preclinical or early stages of the disease prior to plaque deposition. In this study, we report that the inflammatory mediator S100A8 is increased with aging in the mouse brain. It is observed as extracellular aggregates, which do not correspond to corpora amylacea. S100A8 aggregation is enhanced in the hippocampi of two different mouse models for amyloid-β (Aβ) overproduction (Tg2576 and TgAPParctic mice). S100A8 aggregates are seen prior the formation of Aβ plaques and do not colocalize. In vitro treatment of glial cells from primary cultures with Aβ42 resulted in an increased production of S100A8. In parallel, treatment of a neuronal cell line with recombinant S100A8 protein resulted in enhanced Aβ42 and decreased Aβ40 production. Our results suggest that important inflammatory processes are occurring prior to Aβ deposition and the existence of a positive feedback between S100A8 and Aβ productions. The possible relevance of aging- or AD-dependent formation of S100A8 aggregates in the hippocampus thus affecting learning and memory processes is discussed.
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Lodeiro
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Elena
authors.initials: E
authors.lastname: Puerta
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Muhammad-Al-Mustafa
authors.initials: MA
authors.lastname: Ismail
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rodriguez-Rodriguez
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Annica
authors.initials: A
authors.lastname: Rönnbäck
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Alina
authors.initials: A
authors.lastname: Codita
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cristina
authors.initials: C
authors.lastname: Parrado-Fernandez
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Silvia
authors.initials: S
authors.lastname: Maioli
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.|Division of Neurosciences, Department of Cellular and Molecular Neuropharmacology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gil-Bea
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Paula
authors.initials: P
authors.lastname: Merino-Serrais
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Angel
authors.initials: A
authors.lastname: Cedazo-Minguez
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis; D000818:Animals; D040501:Calgranulin A / Q000378:metabolism / Q000502:physiology*; D025461:Feedback, Physiological; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D066263:Protein Aggregation, Pathological
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D040501:Calgranulin A; C086145:S100a8 protein, mouse
keywords: Alzheimer’s disease; Amyloid beta; Corpora amylacea; Neuroinflammation; S100A8