title: An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome: a proteomics approach.
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.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, and.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenini
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, and; Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Fiorini
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, and.
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
authors.affiliation: Division of Nephrology, Department of Medicine and Proteomics Center, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.affiliation: Division of Nephrology, Department of Medicine and Proteomics Center, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Klein
authors.affiliation: Department of Molecular and Biomedical Pharmacology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, and. Electronic address: dabcns@uky.edu.
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000293:Adolescent; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002853:Chromatography, Liquid; D004314:Down Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: Alzheimer disease; Down syndrome; Free radicals; Neuropathology; Proteomics; Trisomy 21