When we worked on Down Syndrome brain in the past we have been focus ing on adult brain. This was a major step forwards as most work on Down Syndrome was carried out on fibroblasts or other tissues and, moreover, we introduced proteomics to identify and quantify brain protein expression. We considered evaluation of brain protein expression in Down Syndrome brain by and by more important than gene hunting at the nucleic acid level realiz ing the long unpredictable way from RNA to protein. The availability of fetal samples along with the proteomic appproach stimulated and reinforced studies on Down Syndrome brain. And indeed, it was found out that some observations on aberrant protein expression in adult Down Syndrome brain could not be verified in the fetal samples indi cating that neurodegeneration in adult Down Syndrome brain may have been responsible rather than trisomy 21. Using brains from the early second trimester of gestation led to the generation of a series of clues for the under standing of aberrant wiring of the brain in Down Syndrome and enabled the determination of altered key functions in early life; e. g. undetectably low drebrin was observed in Down Syndrome cortex, an integral constituent and marker for dendritic spines, main effectors of cross-talk between neurons. In addition, evaluation of the nature of the neuronal deficits in terms of neuro transmission markers could be established as well as neuronal density in fetal Down Syndrome cortex.

When we worked on Down Syndrome brain in the past we have been focus ing on adult brain. This was a major step forwards as most work on Down Syndrome was carried out on fibroblasts or other tissues and, moreover, we introduced proteomics to identify and quantify brain protein expression. We considered evaluation of brain protein expression in Down Syndrome brain by and by more important than gene hunting at the nucleic acid level realiz ing the long unpredictable way from RNA to protein. The availability of fetal samples along with the proteomic appproach stimulated and reinforced studies on Down Syndrome brain. And indeed, it was found out that some observations on aberrant protein expression in adult Down Syndrome brain could not be verified in the fetal samples indi cating that neurodegeneration in adult Down Syndrome brain may have been responsible rather than trisomy 21. Using brains from the early second trimester of gestation led to the generation of a series of clues for the under standing of aberrant wiring of the brain in Down Syndrome and enabled the determination of altered key functions in early life; e. g. undetectably low drebrin was observed in Down Syndrome cortex, an integral constituent and marker for dendritic spines, main effectors of cross-talk between neurons. In addition, evaluation of the nature of the neuronal deficits in terms of neuro transmission markers could be established as well as neuronal density in fetal Down Syndrome cortex.

This book contains updated reviews and original research work on Down Syndrome focussing on brandnew results in neurobiology, in particular results on gene hunting (subtractive hybridization, differential display) and neurochemistry. The book provides new data such as a subtractive library of Down Syndrome brain showing cDNAs that are overexpressed or downregulated and can be regarded as a source for further research on the preliminary transcriptional data given. A 2D-electrophoretic map of human brain proteins including Down Syndrome brain protein expression established by in-gel-digestion of spots with subsequent MALDI-identification provides the scientific basis for protein work to the neuroscientist. Altogether, the book provides a series of new candidate genes possibly involved in Down Syndrome neurobiology, tools for neuroscience studies on Down Syndrome brain thus serving as a manual and updated views and aspects on Down Syndrome pathobiology.

The Neurobiology of Aging and Alzheimer Disease in Down Syndrome provides a multidisciplinary approach to the understanding of aging and Alzheimer disease in Down syndrome that is synergistic and focused on efforts to understand the neurobiology as it pertains to interventions that will slow or prevent disease. The book provides detailed knowledge of key molecular aspects of aging and neurodegeneration in Down Syndrome by bringing together different models of the diseases and highlighting multiple techniques. Additionally, it includes case studies and coverage of neuroimaging, neuropathological and biomarker changes associated with these cohorts. This is a must-have resource for researchers who work with or study aging and Alzheimer disease either in the general population or in people with Down syndrome, for academic and general physicians who interact with sporadic dementia patients and need more information about Down syndrome, and for new investigators to the aging and Alzheimer/Down syndrome arena. - Discusses the complexities involved with aging and Alzheimer's disease in Down syndrome - Summarizes the neurobiology of aging that requires management in adults with DS and leads to healthier aging and better quality of life into old age - Serves as learning tool to orient researchers to the key challenges and offers insights to help establish critical areas of need for further research

Research on the multiple aspects of cognitive impairment in Down syndrome (DS), from genes to behavior to treatment, has made tremendous progress in the last decade. The study of congenital intellectual disabilities such as DS is challenging since they originate from the earliest stages of development and both the acquisition of cognitive skills and neurodegenerative pathologies are cumulative. Comorbidities such as cardiac malformations, sleep apnea, diabetes and dementia are frequent in the DS population, as well, and their increased risk provides a means of assessing early stages of these pathologies that is relevant to the general population. Notably, persons with DS will develop the histopathology of Alzheimer’s disease (formation of neuritic plaques and tangles) and are at high risk for dementia, something that cannot be predicted in the population at large. Identification of the gene encoding the amyloid precursor protein, its localization to chromosome 21 in the 90’s and realization that all persons with DS develop pathology identified this as an important piece of the amyloid cascade hypothesis in Alzheimer’s disease. Awareness of the potential role of people with DS in understanding progression and treatment as well as identification of genetic risk factors and also protective factors for AD is reawakening. For the first time since DS was recognized, major pharmaceutical companies have entered the search for ameliorative treatments, and phase II clinical trials to improve learning and memory are in progress. Enriched environment, brain stimulation and alternative therapies are being tested while clinical assessment is improving, thus increasing the chances of success for therapeutic interventions. Researchers and clinicians are actively pursuing the possibility of prenatal treatments for many conditions, an area with a huge potential impact for developmental disorders such as DS. Our goal here is to present an overview of recent advances with an emphasis on behavioral and cognitive deficits and how these issues change through life in DS. The relevance of comorbidities to the end phenotypes described and relevance of pharmacological targets and possible treatments will be considerations throughout.

Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defense mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important therefore to identify tools for the quantitative analysis of DNA damage in models on neurological disorders. This book presents detailed information on various neurodegenerative disorders and their connection with oxidative stress. This information will provide clinicians with directions to treat these disorders with appropriate therapy and is also of vital importance for the drug industries for the design of new drugs for treatment of degenerative disorders.* Contains the latest information on the subject of neurodegenerative disorders* Reflects on various factors involved in degeneration and gives suggestions for how to tackle these problems

Published since 1959, International Review of Neurobiology is a well-known series appealing to neuroscientists, clinicians, psychologists, physiologists, and pharmacologists. Led by an internationally renowned editorial board, this important serial publishes both eclectic volumes made up of timely reviews and thematic volumes that focus on recent progress in a specific area of neurobiology research. This volume, concentrates on the brain transcriptome.