Plasma based markers of [11C] PiB-PET brain amyloid burden.

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 ma...

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Main Authors: Steven John Kiddle, Madhav Thambisetty, Andrew Simmons, Joanna Riddoch-Contreras, Abdul Hye, Eric Westman, Ian Pike, Malcolm Ward, Caroline Johnston, Michelle Katharine Lupton, Katie Lunnon, Hilkka Soininen, Iwona Kloszewska, Magda Tsolaki, Bruno Vellas, Patrizia Mecocci, Simon Lovestone, Stephen Newhouse, Richard Dobson, Alzheimers Disease Neuroimaging Initiative
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0044260
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author Steven John Kiddle
Madhav Thambisetty
Andrew Simmons
Joanna Riddoch-Contreras
Abdul Hye
Eric Westman
Ian Pike
Malcolm Ward
Caroline Johnston
Michelle Katharine Lupton
Katie Lunnon
Hilkka Soininen
Iwona Kloszewska
Magda Tsolaki
Bruno Vellas
Patrizia Mecocci
Simon Lovestone
Stephen Newhouse
Richard Dobson
Alzheimers Disease Neuroimaging Initiative
author_facet Steven John Kiddle
Madhav Thambisetty
Andrew Simmons
Joanna Riddoch-Contreras
Abdul Hye
Eric Westman
Ian Pike
Malcolm Ward
Caroline Johnston
Michelle Katharine Lupton
Katie Lunnon
Hilkka Soininen
Iwona Kloszewska
Magda Tsolaki
Bruno Vellas
Patrizia Mecocci
Simon Lovestone
Stephen Newhouse
Richard Dobson
Alzheimers Disease Neuroimaging Initiative
author_sort Steven John Kiddle
collection DOAJ
description 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.
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spelling doaj-art-0068a6795ecf429f942edab1cbd38f4b2025-08-20T03:25:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4426010.1371/journal.pone.0044260Plasma based markers of [11C] PiB-PET brain amyloid burden.Steven John KiddleMadhav ThambisettyAndrew SimmonsJoanna Riddoch-ContrerasAbdul HyeEric WestmanIan PikeMalcolm WardCaroline JohnstonMichelle Katharine LuptonKatie LunnonHilkka SoininenIwona KloszewskaMagda TsolakiBruno VellasPatrizia MecocciSimon LovestoneStephen NewhouseRichard DobsonAlzheimers Disease Neuroimaging InitiativeChanges 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.https://doi.org/10.1371/journal.pone.0044260
spellingShingle Steven John Kiddle
Madhav Thambisetty
Andrew Simmons
Joanna Riddoch-Contreras
Abdul Hye
Eric Westman
Ian Pike
Malcolm Ward
Caroline Johnston
Michelle Katharine Lupton
Katie Lunnon
Hilkka Soininen
Iwona Kloszewska
Magda Tsolaki
Bruno Vellas
Patrizia Mecocci
Simon Lovestone
Stephen Newhouse
Richard Dobson
Alzheimers Disease Neuroimaging Initiative
Plasma based markers of [11C] PiB-PET brain amyloid burden.
PLoS ONE
title Plasma based markers of [11C] PiB-PET brain amyloid burden.
title_full Plasma based markers of [11C] PiB-PET brain amyloid burden.
title_fullStr Plasma based markers of [11C] PiB-PET brain amyloid burden.
title_full_unstemmed Plasma based markers of [11C] PiB-PET brain amyloid burden.
title_short Plasma based markers of [11C] PiB-PET brain amyloid burden.
title_sort plasma based markers of 11c pib pet brain amyloid burden
url https://doi.org/10.1371/journal.pone.0044260
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