Abstract
Individuals with trisomy 21, also known as Down syndrome (DS), develop a clinical syndrome including almost identical neuropathological characteristics of Alzheimers disease (AD) observed in non-DS individuals. The main difference is the early age of onset of AD pathology in individuals with DS, with high incidence of clinical symptoms in the late 40- early 50 years of age. The neuropathology of AD in persons with DS is superimposed with the developmental abnormalities causing alterations of neuronal morphology and function. Despite the ubiquitous occurrence of AD neuropathology, clinical signs of dementia do not occur in all adults with DS even at older ages. Phenotype analysis of DS mouse models has revealed a differential age-related neurodegenerative pattern that correlates with specific biochemical and molecular alterations at the cellular level. In fact, several individual genes found in trisomy in DS have been functionally related to neuronal degeneration. Thus, mouse models overexpressing HSA21 gene(s) are fundamental to understand the neurodegenerative process in DS, as described in the present review. In addition, these models might allow to define and evaluate potential drug targets and to develop therapeutic strategies that may interfere or delay the onset of AD.
Keywords: Down syndrome, Alzheimer's disease, neurodegeneration, HSA21 genes, mouse models
CNS & Neurological Disorders - Drug Targets
Title: Insights from Mouse Models to Understand Neurodegeneration in Down Syndrome
Volume: 9 Issue: 4
Author(s): Cristina Fillat, Mara Dierssen, Maria Martinez de Lagran and Xavier Altafaj
Affiliation:
Keywords: Down syndrome, Alzheimer's disease, neurodegeneration, HSA21 genes, mouse models
Abstract: Individuals with trisomy 21, also known as Down syndrome (DS), develop a clinical syndrome including almost identical neuropathological characteristics of Alzheimers disease (AD) observed in non-DS individuals. The main difference is the early age of onset of AD pathology in individuals with DS, with high incidence of clinical symptoms in the late 40- early 50 years of age. The neuropathology of AD in persons with DS is superimposed with the developmental abnormalities causing alterations of neuronal morphology and function. Despite the ubiquitous occurrence of AD neuropathology, clinical signs of dementia do not occur in all adults with DS even at older ages. Phenotype analysis of DS mouse models has revealed a differential age-related neurodegenerative pattern that correlates with specific biochemical and molecular alterations at the cellular level. In fact, several individual genes found in trisomy in DS have been functionally related to neuronal degeneration. Thus, mouse models overexpressing HSA21 gene(s) are fundamental to understand the neurodegenerative process in DS, as described in the present review. In addition, these models might allow to define and evaluate potential drug targets and to develop therapeutic strategies that may interfere or delay the onset of AD.
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Cite this article as:
Fillat Cristina, Dierssen Mara, Martinez de Lagran Maria and Altafaj Xavier, Insights from Mouse Models to Understand Neurodegeneration in Down Syndrome, CNS & Neurological Disorders - Drug Targets 2010; 9 (4) . https://dx.doi.org/10.2174/187152710791556159
DOI https://dx.doi.org/10.2174/187152710791556159 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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