Acta Neuropathologica

, Volume 118, Issue 4, pp 497–504

Oxidative stress damage and oxidative stress responses in the choroid plexus in Alzheimer’s disease

  • Ester Perez-Gracia
  • Rosa Blanco
  • Margarita Carmona
  • Eva Carro
  • Isidro Ferrer
Original Paper

DOI: 10.1007/s00401-009-0574-4

Cite this article as:
Perez-Gracia, E., Blanco, R., Carmona, M. et al. Acta Neuropathol (2009) 118: 497. doi:10.1007/s00401-009-0574-4

Abstract

Choroid plexus homogenates from 27 cases with Alzheimer disease-related pathology (AD), stages I/0 (n = 5), III–IV/0-B (n = 15) and V–VI/B-C (n = 7) and 3 age-matched controls (no clinical symptoms, no neuropathological lesions) were processed for gel electrophoresis and western blotting for oxidation markers carboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL). Increased CEL and CML expression was seen in AD cases stages IVB, and V–VI/B-C when compared to controls and cases with AD-related pathology classified as I/0 and III/0. Variable stress damage was seen in stage III/B. Although lower stages of AD did not show β-amyloid deposition in the choroid plexus, the amount of β-amyloid was very variable at stages V/VI as revealed by western blotting, suggesting that other factors in addition to local fibrillar β-amyloid were associated with oxidative damage in the choroid plexus. Two-dimensional gel electrophoresis and western blotting to CEL and CML in combination with mass spectrometry disclosed increased intensity of variable spots in AD cases leading to the identification of tyrosine 3/tryptophan 5-monooxygenase activation protein, zeta polypeptide, tropomyosin 3 isoform, and apolipoprotein A-II (ApoA-II) as targets of increased oxidative damage in AD. Oxidation of these proteins may result in impaired protein interactions, protein folding and protein kinase activity; abnormal function of endothelial and vascular smooth muscle cells; and impaired HDL-cholesterol metabolism in the choroid plexus in advanced stages of AD.

Keywords

Alzheimer disease Oxidative damage 14-3-3 Tropomyosin Tyrosine 3/tryptophan 5-monooxygenase Apolipoprotein A-II Choroid plexus 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ester Perez-Gracia
    • 1
  • Rosa Blanco
    • 1
  • Margarita Carmona
    • 1
  • Eva Carro
    • 2
  • Isidro Ferrer
    • 1
  1. 1.Servei Anatomia Patològica, Institut Neuropatologia, CIBERNED, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de LlobregatUniversitat de BarcelonaBarcelonaSpain
  2. 2.Neuroscience Laboratory, Research CenterHospital 12 de Octubre, CIBERNEDMadridSpain

Personalised recommendations