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El pdf del artículo es la versión pre-print.-- et al. ; Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease. Age is the main risk factor for sporadic AD, which is the most prevalent type. Amyloid-β peptide (Aβ) neurotoxicity is the proposed first step in a cascade of deleterious events leading to AD pathology and dementia. Glial cells play an important role in these changes. Astrocytes provide vital support to neurons and modulate functional synapses. Therefore, the toxic effects of Aβ on astrocytes might promote neurodegenerative changes that lead to AD. Aging reduces astrocyte antioxidant defenses and induces oxidative stress. We studied the effects of Aβ {42} on cultures of human astrocytes in the presence or absence of the following pro-oxidant agents: buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, and FeSO{4}, which liberates redox active iron. Pro-oxidant conditions potentiated Aβ toxicity, as shown by the generation of free radicals, inflammatory changes, and apoptosis. Similar treatments were assessed in rats in vivo. A combination of Aβ {40} and Aβ {42} or Aβ {42} alone was infused intracerebroventricularly for 4 weeks. Other animal groups were also infused with BSO and FeSO{4}. A long-term analysis that ended 4 months later showed greater cognitive impairment in the Morris water maze task, which was induced by Aβ plus pro-oxidant agent treatments. Pro-oxidant agents also potentiated brain tissue pathology. This was demonstrated in histological studies that showed highly increased astrocyte reactivity in AD-vulnerable areas, Aβ deposits, and oxidative damage of AD-sensitive hippocampal neurons. To increase our understanding of AD, experimental models should be used that mimic age-related brain changes, in which age-related oxidative stress potentiates the effects of Aβ. © 2010 - IOS Press and the authors. ; This study was supported by grants SAF200613092-C02-02 from the Spanish Ministerio de Ciencia e Innovación, RD06/0013/1004 (RETICEF) from the Instituto de Salud Carlos III, 062931 from Fundació La Marató de TV3 and by the European Network of Excellence DiMI (LSHB-CT-2005-512146). S. García-Matas received a Generalitat (Autonomous Government of Catalonia) fellowship. ; Peer Reviewed

Neuroinflammation is a risk factor for Alzheimer's disease (AD). We sought to study the glial derangement in AD using diverse experimental models and human brain tissue. Besides classical pro-inflammatory cytokines, we analyzed chitinase 3 like 1 (CHI3L1 or YKL40) and triggering receptor expressed on myeloid cells 2 (TREM2) that are increasingly being associated with astrogliosis and microgliosis in AD, respectively. The SAMP8 mouse model of accelerated aging and AD traits showed elevated pro-inflammatory cytokines and activated microglia phenotype. Furthermore, 6-month-old SAMP8 showed an exacerbated inflammatory response to peripheral lipopolysaccharide in the hippocampus and null responsiveness at the advanced age (for this strain) of 12 months. ; This research was funded by Spanish MINECO and European Regional Development Fund, grant number SAF2016- 77703; Spanish MCINN, grant number PID2019-106285RB; Catalan Autonomous Government AGAUR, grant number 2017-SGR-106; Competitiveness Operational Programme 2014-2020, C-Reactive protein therapy for stroke-associated dementia, ID P_37_674, MySMIS code: 103432, contract 51/05.09.2016; and the CERCA Programme/Generalitat de Catalunya. RCo was supported by a post-doctoral research contract of the Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. AL (PERIS SLT008/18/00061) received funding from Departament de Salut de la Generalitat de Catalunya. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).