title: Blood-borne amyloid-beta dimer correlates with clinical markers of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common age-related dementia. Unfortunately due to a lack of validated biomarkers definitive diagnosis relies on the histological demonstration of amyloid-beta (Abeta) plaques and tau neurofibrillary tangles. Abeta processing is implicated in AD progression and many therapeutic strategies target various aspects of this biology. While Abeta deposition is the most prominent feature of AD, oligomeric forms of Abeta have been implicated as the toxic species inducing the neuronal dysfunction. Currently there are no methods allowing routine monitoring of levels of such species in living populations. We have used surface enhanced laser desorption ionization time of flight (SELDI-TOF) mass spectrometry incorporating antibody capture to investigate whether the cellular membrane-containing fraction of blood provides a new source of biomarkers. There are significant differences in the mass spectra profiles of AD compared with HC subjects, with significantly higher levels of Abeta monomer and dimer in the blood of AD subjects. Furthermore, levels of these species correlated with clinical markers of AD including brain Abeta burden, cognitive impairment and brain atrophy. These results indicate that fundamental biochemical events relevant to AD can be monitored in blood, and that the species detected may be useful clinical biomarkers for AD.
authors.affiliation: Mental Health Research Institute, The University of Melbourne, Parkville, Melbourne, Victoria 3052, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Keyla A
authors.initials: KA
authors.lastname: Perez
authors.forename: Kerryn E
authors.initials: KE
authors.lastname: Pike
authors.forename: W Mei
authors.initials: WM
authors.lastname: Kok
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.forename: Anthony R
authors.initials: AR
authors.lastname: White
authors.forename: Pierrick
authors.initials: P
authors.lastname: Bourgeat
authors.forename: Olivier
authors.initials: O
authors.lastname: Salvado
authors.forename: Justin
authors.initials: J
authors.lastname: Bedo
authors.forename: Craig A
authors.initials: CA
authors.lastname: Hutton
authors.forename: Noel G
authors.initials: NG
authors.lastname: Faux
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Barnham
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis* / Q000000981:diagnostic imaging; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D055503:Protein Multimerization; D011877:Radionuclide Imaging; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers
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