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Comparative Study
, 76, 89-95

An Investigation of the Molecular Mechanisms Engaged Before and After the Development of Alzheimer Disease Neuropathology in Down Syndrome: A Proteomics Approach

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Comparative Study

An Investigation of the Molecular Mechanisms Engaged Before and After the Development of Alzheimer Disease Neuropathology in Down Syndrome: A Proteomics Approach

Giovanna Cenini et al. Free Radic Biol Med.

Abstract

Down syndrome (DS) is one of the most common causes of intellectual disability, owing to trisomy of all or part of chromosome 21. DS is also associated with the development of Alzheimer disease (AD) neuropathology after the age of 40 years. To better clarify the cellular and metabolic pathways that could contribute to the differences in DS brain, in particular those involved in the onset of neurodegeneration, we analyzed the frontal cortex of DS subjects with or without significant AD pathology in comparison with age-matched controls, using a proteomics approach. Proteomics represents an advantageous tool to investigate the molecular mechanisms underlying the disease. From these analyses, we investigated the effects that age, DS, and AD neuropathology could have on protein expression levels. Our results show overlapping and independent molecular pathways (including energy metabolism, oxidative damage, protein synthesis, and autophagy) contributing to DS, to aging, and to the presence of AD pathology in DS. Investigation of pathomechanisms involved in DS with AD may provide putative targets for therapeutic approaches to slow the development of AD.

Keywords: Alzheimer disease; Down syndrome; Free radicals; Neuropathology; Proteomics; Trisomy 21.

Figures

Fig. 1
Fig. 1. 2D protein expression maps
Proteomic profile of representative 2D-gels with proteins differently expressed in four groups of matching: young healthy CTR group vs young DS group (A), old healthy CTR group vs DS subjects with AD-like dementia (B), DS group vs DSAD group (C), and young healthy CTR group vs old healthy CTR group (D). The identified proteins by mass spectrometry are reported.
Fig. 2
Fig. 2. Venn diagram on overlapping proteins between the four different groups of analysis

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