title: Plasma based markers of [11C] PiB-PET brain amyloid burden.
abstract: Changes in brain amyloid burden have been shown to relate to Alzheimer's disease pathology, and are believed to precede the development of cognitive decline. There is thus a need for inexpensive and non-invasive screening methods that are able to accurately estimate brain amyloid burden as a marker of Alzheimer's disease. One potential method would involve using demographic information and measurements on plasma samples to establish biomarkers of brain amyloid burden; in this study data from the Alzheimer's Disease Neuroimaging Initiative was used to explore this possibility. Sixteen of the analytes on the Rules Based Medicine Human Discovery Multi-Analyte Profile 1.0 panel were found to associate with [(11)C]-PiB PET measurements. Some of these markers of brain amyloid burden were also found to associate with other AD related phenotypes. Thirteen of these markers of brain amyloid burden--c-peptide, fibrinogen, alpha-1-antitrypsin, pancreatic polypeptide, complement C3, vitronectin, cortisol, AXL receptor kinase, interleukin-3, interleukin-13, matrix metalloproteinase-9 total, apolipoprotein E and immunoglobulin E--were used along with co-variates in multiple linear regression, and were shown by cross-validation to explain >30% of the variance of brain amyloid burden. When a threshold was used to classify subjects as PiB positive, the regression model was found to predict actual PiB positive individuals with a sensitivity of 0.918 and a specificity of 0.545. The number of APOE [Symbol: see text] 4 alleles and plasma apolipoprotein E level were found to contribute most to this model, and the relationship between these variables and brain amyloid burden was explored.
authors.affiliation: National Institute of Health Research Biomedical Research Centre for Mental Health, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom. steven.kiddle@kcl.ac.uk
authors.forename: Steven John
authors.initials: SJ
authors.lastname: Kiddle
authors.forename: Madhav
authors.initials: M
authors.lastname: Thambisetty
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.forename: Joanna
authors.initials: J
authors.lastname: Riddoch-Contreras
authors.forename: Abdul
authors.initials: A
authors.lastname: Hye
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
authors.forename: Ian
authors.initials: I
authors.lastname: Pike
authors.forename: Malcolm
authors.initials: M
authors.lastname: Ward
authors.forename: Caroline
authors.initials: C
authors.lastname: Johnston
authors.forename: Michelle Katharine
authors.initials: MK
authors.lastname: Lupton
authors.forename: Katie
authors.initials: K
authors.lastname: Lunnon
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Iwona
authors.initials: I
authors.lastname: Kloszewska
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.forename: Stephen
authors.initials: S
authors.lastname: Newhouse
authors.forename: Richard
authors.initials: R
authors.lastname: Dobson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016000:Cluster Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011379:Prognosis; D015203:Reproducibility of Results; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D015415:Biomarkers; D013844:Thiazoles