Microglial brain region−dependent diversity and selective regional sensitivities to aging

Microglia play critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific spatially-restricted patterns, the origins of which are unknown. We performed the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse and reveal that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during ageing. Microglial diversity may enable regionally localised homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration

Genetic testing and common disorders in a public health framework: how to assess relevance and possibilities

This paper discusses genetic testing and common disorders from a health-care perspective. New possibilities for genetic testing confront health-care workers with the question of whom to test and which test to use. This document focuses on genetic testing and screening in common disorders. The term ¿common disorder¿ is used for disorders that individually have a high impact on public health.Examples of common disorders include cardiovascular disease (CVD), stroke, diabetes, cancer, dementia, and depression. For a health-care practitioner ¿ unlike a geneticist or an epidemiologist ¿ it may not be clear whether a common disorder is due to one gene with a high risk of serious disease, or due to a combination of several genes and several environmental factors. This document will not consider germline prenatal or preconceptional testing, nor testing of biomarkers for tumor recurrence, but it will discuss testing of mutations in tumor tissue, since this may reveal susceptibility to certain forms of therapy. Also, pharmacogenomic applications will not be discussed in depth, although some examples will be given of pharmacogenomic testing. The outlne is as following: First, the terrain of common complex disorders is introduced. Different assessment frames for genetic testing and screening are discussed. The section following that examines the aims and strategies for genetic testing and screening in common disorders and discusses some examples of current testing and screening in Europe. The section ¿The economic evaluation of genetic tests¿ discusses the cost¿benefit relation of different types of tests and screening strategies and how they could be used in the clinic in a cost-effective way. The subsequent section addresses the ethical, legal, and social issues of testing and screening in common disorders. The last section addresses regulatory and intellectual property issues in the EU as well as the United States.JRC.DDG.J.2-The economics of climate change, energy and transpor