Aggregation of the Inflammatory S100A8 Precedes Aβ Plaque Formation in Transgenic APP Mice: Positive Feedback for S100A8 and Aβ Productions
Autor: | Muhammad-Al-Mustafa Ismail, Cristina Parrado-Fernandez, Alina Codita, Paula Merino-Serrais, Silvia Maioli, Maria Lodeiro, Elena Puerta, Patricia Rodriguez-Rodriguez, Annica Rönnbäck, Angel Cedazo-Minguez, Francisco J. Gil-Bea |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Aging Amyloid Amyloid beta Inflammation Mice Transgenic Hippocampus Protein Aggregation Pathological S100A8 03 medical and health sciences Amyloid beta-Protein Precursor Mice 0302 clinical medicine Alzheimer Disease medicine Extracellular Animals Calgranulin A Neuroinflammation Feedback Physiological Amyloid beta-Peptides biology Age Factors Cell biology 030104 developmental biology Cell culture Immunology biology.protein Geriatrics and Gerontology medicine.symptom Corpora amylacea 030217 neurology & neurosurgery |
Zdroj: | The journals of gerontology. Series A, Biological sciences and medical sciences. 72(3) |
ISSN: | 1758-535X |
Popis: | 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. |
Databáze: | OpenAIRE |
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