An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome: A proteomics approach

Giovanna Cenini; Ada Fiorini; Rukhsana Sultana; Marzia Perluigi; Jian Cai; Jon B. Klein; Elizabeth Head; D. Allan Butterfield

doi:10.1016/j.freeradbiomed.2014.08.006

An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome: A proteomics approach

Giovanna Cenini, Ada Fiorini, Rukhsana Sultana, Marzia Perluigi, Jian Cai, Jon B. Klein, Elizabeth Head, D. Allan Butterfield

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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.

Original language	English
Pages (from-to)	89-95
Number of pages	7
Journal	Free Radical Biology and Medicine
Volume	76
DOIs	https://doi.org/10.1016/j.freeradbiomed.2014.08.006
State	Published - Nov 2014

Bibliographical note

Publisher Copyright:
© 2014 Elsevier Inc.

Funding

This work was supported in part by grants from the National Institutes of Health (NIH) to D.A.B. ( AG-05119 ) and to E.H. from the National Institute of Child Health and Human Development (NICHD; HD-064993 ). Additional funding was provided by the NIH to the UCI ADRC ( P50 AG16573 ) and to the UK ADC (P30 AG028383). Human tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland (Baltimore, MD, USA) under Contract HHSN275200900011C, Ref. No. N01-HD-9–0011.

Funders	Funder number
National Institutes of Health (NIH)	AG-05119
National Institutes of Health (NIH)
NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research	R01HD064993
NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research
Alzheimer's Disease Research Center, Emory University	P30 AG028383, P50 AG16573
Alzheimer's Disease Research Center, Emory University

Keywords

Alzheimer disease
Down syndrome
Free radicals
Neuropathology
Proteomics
Trisomy 21

ASJC Scopus subject areas

Biochemistry
Physiology (medical)

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10.1016/j.freeradbiomed.2014.08.006

Cite this

Cenini, G., Fiorini, A., Sultana, R., Perluigi, M., Cai, J., Klein, J. B., Head, E., & Butterfield, D. A. (2014). An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome: A proteomics approach. Free Radical Biology and Medicine, 76, 89-95. https://doi.org/10.1016/j.freeradbiomed.2014.08.006

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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.",

keywords = "Alzheimer disease, Down syndrome, Free radicals, Neuropathology, Proteomics, Trisomy 21",

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doi = "10.1016/j.freeradbiomed.2014.08.006",

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Cenini, G, Fiorini, A, Sultana, R, Perluigi, M, Cai, J, Klein, JB, Head, E & Butterfield, DA 2014, 'An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome: A proteomics approach', Free Radical Biology and Medicine, vol. 76, pp. 89-95. https://doi.org/10.1016/j.freeradbiomed.2014.08.006

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AU - Fiorini, Ada

AU - Sultana, Rukhsana

AU - Perluigi, Marzia

AU - Cai, Jian

AU - Klein, Jon B.

AU - Head, Elizabeth

AU - Butterfield, D. Allan

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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

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KW - Trisomy 21

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An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome: A proteomics approach

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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