Detalle Publicación

ARTÍCULO
Aggregation of the inflammatory S100A8 precedes Aß plaque formation in transgenic APP mice: positive feedback for S100A8 and Aß productions
Autores: Lodeiro, M.; Puerta Ruiz de Azua, Elena; Ismail, M. A.; Rodríguez Rodríguez, Patricia; Rönnbäck, A.; Codita, A.; Parrado-Fernandez, C.; Maioli, S.; Gil Bea, Francisco Javier; Merino-Serrais, P.; Cedazo-Minguez, A.
Título de la revista: JOURNALS OF GERONTOLOGY SERIES A -BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
ISSN: 1079-5006
Volumen: 72
Número: 3
Páginas: 319 - 328
Fecha de publicación: 2017
Resumen:
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-ß (Aß) overproduction (Tg2576 and TgAPParctic mice). S100A8 aggregates are seen prior the formation of Aß plaques and do not colocalize. In vitro treatment of glial cells from primary cultures with Aß42 resulted in an increased production of S100A8. In parallel, treatment of a neuronal cell line with recombinant S100A8 protein resulted in enhanced Aß42 and decreased Aß40 production. Our results suggest that important inflammatory processes are occurring prior to Aß deposition and the existence of a positive feedback between S100A8 and Aß productions. The possible relevance of aging- or AD-dependent formation of S100A8 aggregates in the hippocampus thus affecting learning and memory processes is discussed.