TY - JOUR
T1 - An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome
T2 - A proteomics approach
AU - Cenini, Giovanna
AU - Fiorini, Ada
AU - Sultana, Rukhsana
AU - Perluigi, Marzia
AU - Cai, Jian
AU - Klein, Jon B.
AU - Head, Elizabeth
AU - Butterfield, D. Allan
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/11
Y1 - 2014/11
N2 - 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.
AB - 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.
KW - Alzheimer disease
KW - Down syndrome
KW - Free radicals
KW - Neuropathology
KW - Proteomics
KW - Trisomy 21
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U2 - 10.1016/j.freeradbiomed.2014.08.006
DO - 10.1016/j.freeradbiomed.2014.08.006
M3 - Article
C2 - 25151119
AN - SCOPUS:84907176725
SN - 0891-5849
VL - 76
SP - 89
EP - 95
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -