Association between frontal cortex oxidative damage and beta-amyloid as a function of age in Down syndrome

Cesare Mancuso, Eugenio Barone, Giovanna Cenini, Amy L.S. Dowling, Tina L. Beckett, Michael Paul Murphy, Harry Levine, Ira T. Lott, Frederick A. Schmitt, D. Allan Butterfield, Elizabeth Head

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

75 Citazioni (Scopus)

Abstract

Down syndrome (DS) is the most common genetic cause of intellectual disability in children, and the number of adults with DS reaching old age is increasing. By the age of 40 years, virtually all people with DS have sufficient neuropathology for a postmortem diagnosis of Alzheimer disease (AD). Trisomy 21 in DS leads to an overexpression of many proteins, of which at least two are involved in oxidative stress and AD: superoxide dismutase 1 (SOD1) and amyloid precursor protein (APP). In this study, we tested the hypothesis that DS brains with neuropathological hallmarks of AD have more oxidative and nitrosative stress than those with DS but without significant AD pathology, as compared with similarly aged-matched non-DS controls. The frontal cortex was examined in 70 autopsy cases (n=29 control and n=41 DS). By ELISA, we quantified soluble and insoluble Aβ40 and Aβ42, as well as oligomers. Oxidative and nitrosative stress levels (protein carbonyls, 4-hydroxy-2-trans-nonenal (HNE)-bound proteins, and 3-nitrotyrosine) were measured by slot-blot. We found that soluble and insoluble amyloid beta peptide (Aβ) and oligomers increase as a function of age in DS frontal cortex. Of the oxidative stress markers, HNE-bound proteins were increased overall in DS. Protein carbonyls were correlated with Aβ40 levels. These results suggest that oxidative damage, but not nitrosative stress, may contribute to the onset and progression of AD pathogenesis in DS. Conceivably, treatment with antioxidants may provide a point of intervention to slow pathological alterations in DS.
Lingua originaleEnglish
pagine (da-a)130-138
Numero di pagine9
RivistaBIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE
Volume1822
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • Down syndrome
  • beta-amyloid

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