Estrés oxidativo, respuesta inmune, plasticidad sináptica y cognición en modelos transgénicos de la enfermedad de Alzheimer / Oxidative stress, the immune response, synaptic plasticity, and cognition in transgenic models of Alzheimer disease

Introducción: En el mundo, alrededor de 50 millones de personas padecen demencia; la forma más común es la enfermedad de Alzheimer (EA), que representa el 60-70% de los casos. Dada su alta incidencia, se hace imperativo diseñar estudios que permitan ampliar el conocimiento sobre su aparición y desarrollo, para proponer diagnósticos tempranos y/o posibles tratamientos. Una de las estrategias metodológicas que se han desarrollado son los modelos transgénicos murinos para el estudio de los factores involucrados en su etiología, y entre ellos, el estrés oxidativo y la respuesta inmune.DesarrolloSe realizó una búsqueda de artículos originales y revisiones en PubMed, Scopus y Google Scholar (2013-2019). En esta revisión abordamos dos factores que han sido estudiados de forma independiente: el estrés oxidativo y la respuesta inmune en modelos transgénicos para la EA, y se discute la relación que existe entre ellos y que impacta en la pérdida de la plasticidad sináptica y estructural, produciendo como efecto final el deterioro cognitivo.ConclusiónEsta revisión describe posibles mecanismos en donde participan el estrés oxidativo y la respuesta inmune sobre los efectos moleculares, celulares y conductuales en la EA, observando una estrecha relación entre estos elementos que conducen hacia el deterioro cognitivo. (AU)

Introduction: Worldwide, approximately 50 million people have dementia, with Alzheimer disease (AD) being the most common type, accounting for 60%-70% of cases. Given its high incidence, it is imperative to design studies to expand our knowledge about its onset and development, and to develop early diagnosis strategies and/or possible treatments. One methodological strategy is the use of transgenic mouse models for the study of the factors involved in AD aetiology, which include oxidative stress and the immune response.DevelopmentWe searched the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2013 and 2019. In this review, we address two factors that have been studied independently, oxidative stress and the immune response, in transgenic models of AD, and discuss the relationship between these factors and their impact on the loss of synaptic and structural plasticity, resulting in cognitive impairment.ConclusionThis review describes possible mechanisms by which oxidative stress and the immune response participate in the molecular, cellular, and behavioural effects of AD, observing a close relationship between these factors, which lead to cognitive impairment. (AU)

Oxidative stress, the immune response, synaptic plasticity, and cognition in transgenic models of Alzheimer disease. / Estrés oxidativo, respuesta inmune, plasticidad sináptica y cognición en modelos transgénicos de la enfermedad de Alzheimer.

INTRODUCTION: Worldwide, approximately 50 million people have dementia, with Alzheimer disease (AD) being the most common type, accounting for 60%-70% of cases. Given its high incidence, it is imperative to design studies to expand our knowledge about its onset and development, and to develop early diagnosis strategies and/or possible treatments. One methodological strategy is the use of transgenic mouse models for the study of the factors involved in AD aetiology, which include oxidative stress and the immune response. DEVELOPMENT: We searched the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2013 and 2019. In this review, we address two factors that have been studied independently, oxidative stress and the immune response, in transgenic models of AD, and discuss the relationship between these factors and their impact on the loss of synaptic and structural plasticity, resulting in cognitive impairment. CONCLUSION: This review describes possible mechanisms by which oxidative stress and the immune response participate in the molecular, cellular, and behavioural effects of AD, observing a close relationship between these factors, which lead to cognitive impairment.

Oxidative stress, the immune response, synaptic plasticity, and cognition in transgenic models of Alzheimer disease.

INTRODUCTION: Worldwide, approximately 50 million people have dementia, with Alzheimer disease (AD) being the most common type, accounting for 60%-70% of cases. Given its high incidence, it is imperative to design studies to expand our knowledge about its onset and development, and to develop early diagnosis strategies and/or possible treatments. One methodological strategy is the use of transgenic mouse models for the study of the factors involved in AD aetiology, which include oxidative stress and the immune response. DEVELOPMENT: We searched the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2013 and 2019. In this review, we address 2 factors that have been studied independently, oxidative stress and the immune response, in transgenic models of AD, and discuss the relationship between these factors and their impact on the loss of synaptic and structural plasticity, resulting in cognitive impairment. CONCLUSION: This review describes possible mechanisms by which oxidative stress and the immune response participate in the molecular, cellular, and behavioural effects of AD, observing a close relationship between these factors, which lead to cognitive impairment.

Anti-islet autoantibodies detected by monoclonal antibody 1A2: further studies suggesting a role in the pathogenesis of IDDM.

Insulin-dependent diabetes mellitus (IDDM) is associated with autoantibodies to several pancreatic islet antigens. We have described an assay in which autoantibodies displace a radiolabelled monoclonal anti-islet antibody. Sera from 87% of 429 children at time of diagnosis of IDDM were positive, while sera from control groups had much lower prevalences (1.3-19%). Sera from 41.9% of diabetic subjects remained positive after 20 years duration of IDDM. Sera from 23.6% of parents and 37.9% of non-diabetic siblings were positive. Twenty relatives who subsequently developed IDDM had the same prevalence of the antibodies (85%) as did the patients at time of diagnosis. These findings confirm that the autoantibodies detected by monoclonal antibody (mAb) 1A2 are common at the onset of IDDM and their presence prior to the onset of hyperglycaemia suggests that this method may be useful in screening non-diabetic populations. The high prevalence of antibodies in relatives reduces the efficacy for diabetes prediction, but suggests either that generation of these antibodies is an autosomal dominant trait, or that the antigen detected by these antibodies is cross-reactive with a common environmental antigen. Differentiation between these hypotheses will await the identification of the specific islet-cell antigen detected by mAb 1A2.