Oxidative stress damage and oxidative stress responses in the choroid plexus in Alzheimer's disease.
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 beta-amyloid deposition in the choroid plexus, the amount of beta-amyloid was very variable at stages V/VI as revealed by western blotting, suggesting that other factors in addition to local fibrillar beta-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.
Perez-Gracia
Ester
E
Servei Anatomia Patològica, Institut Neuropatologia, CIBERNED, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Universitat de Barcelona, Carrer Feixa LLarga sn, Barcelona, Spain.
Blanco
Rosa
R
Carmona
Margarita
M
Carro
Eva
E
Ferrer
Isidro
I
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015153:Blotting, Western; D002831:Choroid Plexus / Q000378:metabolism / Q000473:pathology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D011506:Proteins