A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort

Steve Pedrini; Veer Bala Gupta; Eugene Hone; James D. Doecke; Sid E. O'Bryant; Ian R. James; Ashley I. Bush; Christopher C. Rowe; Victor L. Villemagne; David J. Ames; Colin L. Masters; Ralph N. Martins; AIBL Research Group; Gregory R. Savage; Bill Wilson; Pierrick T. Bourgeat; Jürgen Fripp; Simon Gibson; Hugo Leroux; Simon J. McBride; Olivier Salvado; Michael Felix Fenech; Maxime François; Mary B. Barnes; Jenalle E. Baker; Kevin Jeffrey Barnham; Shayne A. Bellingham; Julia Bomke; Svetlana Bozin Pejoska; Rachel F. Buckley; Lesley Cheng; Steven John Collins; Ian Cooke; Elizabeth V. Cyarto; David G. Darby; Vincent Doré; Denise El-Sheikh; Noel G. Faux; Christopher J. Fowler; Karra D. Harrington; Andrew F. Hill; Malcolm Kenneth Horne; Gareth R. Jones; Adrian Kamer; Neil Killeen; Hannah Korrel; Fiona Lamb; Nicola T. Lautenschlager; Kate Lennon; Qiaoxin Li; Yen Ying Lim; Andrea G. Louey; Lance S. Macaulay; Lucy Mackintosh; Paul T. Maruff; Alissandra M. McIlroy; Julie Nigro; Keyla A. Perez; Kelly Kathleen Pertile; Carolina Restrepo; Barbara Rita Cardoso; Alan R. Rembach; Blaine R. Roberts; Joanne S. Robertson; Rebecca L. Rumble; Timothy M. Ryan; Jack Sach; Brendan S. Silbert; Christine Thai; Brett O. Trounson; Irene Volitakis; Michael Vovos; Larry Ward; Andrew D. Watt; Robert Williams; Michael Clifford Woodward.; Paul A. Yates; Fernanda Yevenes Ugarte; Ping Zhang; Sabine M. Bird; Belinda Brown; Samantha C. Burnham; Pratishtha Chatterjee; Kay L. Cox; Shane Fernandez; Warnakulasuriya M.A.D.B. Fernando; Samantha L. Gardener; Simon M. Laws; Florence Lim; Lucy Lim; Michelle L. Tegg; Kathy Lucas; Georgia Martins; Tenielle Porter; Stephanie R. Rainey-Smith; Mark A. Rodrigues; Kaikai Shen; Hamid R. Sohrabi; Kevin Taddei; Tania Taddei; Sherilyn Tan; Giuseppe Verdile; Michael Weinborn; Maree Farrow; Shaun M. Frost; David Hanson; Maryam Hor; Yogesan Kanagasingam; Wayne Richard Leifert; Linda Jane Lockett; Malcolm Riley; Ian W. Saunders; Philip Thomas

doi:10.1038/s41598-017-14020-9

A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort

Steve Pedrini, Veer Bala Gupta, Eugene Hone, James D. Doecke, Sid E. O'Bryant, Ian R. James, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David J. Ames, Colin L. Masters, Ralph N. Martins, AIBL Research Group, Gregory R. Savage, Bill Wilson, Pierrick T. Bourgeat, Jürgen Fripp, Simon Gibson, Hugo Leroux, Simon J. McBrideOlivier Salvado, Michael Felix Fenech, Maxime François, Mary B. Barnes, Jenalle E. Baker, Kevin Jeffrey Barnham, Shayne A. Bellingham, Julia Bomke, Svetlana Bozin Pejoska, Rachel F. Buckley, Lesley Cheng, Steven John Collins, Ian Cooke, Elizabeth V. Cyarto, David G. Darby, Vincent Doré, Denise El-Sheikh, Noel G. Faux, Christopher J. Fowler, Karra D. Harrington, Andrew F. Hill, Malcolm Kenneth Horne, Gareth R. Jones, Adrian Kamer, Neil Killeen, Hannah Korrel, Fiona Lamb, Nicola T. Lautenschlager, Kate Lennon, Qiaoxin Li, Yen Ying Lim, Andrea G. Louey, Lance S. Macaulay, Lucy Mackintosh, Paul T. Maruff, Alissandra M. McIlroy, Julie Nigro, Keyla A. Perez, Kelly Kathleen Pertile, Carolina Restrepo, Barbara Rita Cardoso, Alan R. Rembach, Blaine R. Roberts, Joanne S. Robertson, Rebecca L. Rumble, Timothy M. Ryan, Jack Sach, Brendan S. Silbert, Christine Thai, Brett O. Trounson, Irene Volitakis, Michael Vovos, Larry Ward, Andrew D. Watt, Robert Williams, Michael Clifford Woodward., Paul A. Yates, Fernanda Yevenes Ugarte, Ping Zhang, Sabine M. Bird, Belinda Brown, Samantha C. Burnham, Pratishtha Chatterjee, Kay L. Cox, Shane Fernandez, Warnakulasuriya M.A.D.B. Fernando, Samantha L. Gardener, Simon M. Laws, Florence Lim, Lucy Lim, Michelle L. Tegg, Kathy Lucas, Georgia Martins, Tenielle Porter, Stephanie R. Rainey-Smith, Mark A. Rodrigues, Kaikai Shen, Hamid R. Sohrabi, Kevin Taddei, Tania Taddei, Sherilyn Tan, Giuseppe Verdile, Michael Weinborn, Maree Farrow, Shaun M. Frost, David Hanson, Maryam Hor, Yogesan Kanagasingam, Wayne Richard Leifert, Linda Jane Lockett, Malcolm Riley, Ian W. Saunders, Philip Thomas

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Abstract

Alzheimer's Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer's participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ϵ4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ϵ4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.

Original language	English
Article number	14057
Number of pages	12
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-14020-9
Publication status	Published - 25 Oct 2017
Externally published	Yes

Bibliographical note

(CC-BY 4.0) Open Access article licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license (http://creativecommons.org/licenses/by/4.0) .

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Published versionFinal published version, 1.44 MBLicence: CC BY

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Pedrini, S., Gupta, V. B., Hone, E., Doecke, J. D., O'Bryant, S. E., James, I. R., Bush, A. I., Rowe, C. C., Villemagne, V. L., Ames, D. J., Masters, C. L., Martins, R. N., AIBL Research Group, Savage, G. R., Wilson, B., Bourgeat, P. T., Fripp, J., Gibson, S., Leroux, H., ... Thomas, P. (2017). A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort. Scientific Reports, 7(1), Article 14057 . https://doi.org/10.1038/s41598-017-14020-9

@article{ed089136877d4a199c7831c8714eaeca,

title = "A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort",

abstract = "Alzheimer's Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer's participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ϵ4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ϵ4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.",

author = "Steve Pedrini and Gupta, {Veer Bala} and Eugene Hone and Doecke, {James D.} and O'Bryant, {Sid E.} and James, {Ian R.} and Bush, {Ashley I.} and Rowe, {Christopher C.} and Villemagne, {Victor L.} and Ames, {David J.} and Masters, {Colin L.} and Martins, {Ralph N.} and {AIBL Research Group} and Savage, {Gregory R.} and Bill Wilson and Bourgeat, {Pierrick T.} and J{\"u}rgen Fripp and Simon Gibson and Hugo Leroux and McBride, {Simon J.} and Olivier Salvado and Fenech, {Michael Felix} and Maxime Fran{\c c}ois and Barnes, {Mary B.} and Baker, {Jenalle E.} and Barnham, {Kevin Jeffrey} and Bellingham, {Shayne A.} and Julia Bomke and Pejoska, {Svetlana Bozin} and Buckley, {Rachel F.} and Lesley Cheng and Collins, {Steven John} and Ian Cooke and Cyarto, {Elizabeth V.} and Darby, {David G.} and Vincent Dor{\'e} and Denise El-Sheikh and Faux, {Noel G.} and Fowler, {Christopher J.} and Harrington, {Karra D.} and Hill, {Andrew F.} and Horne, {Malcolm Kenneth} and Jones, {Gareth R.} and Adrian Kamer and Neil Killeen and Hannah Korrel and Fiona Lamb and Lautenschlager, {Nicola T.} and Kate Lennon and Qiaoxin Li and Lim, {Yen Ying} and Louey, {Andrea G.} and Macaulay, {Lance S.} and Lucy Mackintosh and Maruff, {Paul T.} and McIlroy, {Alissandra M.} and Julie Nigro and Perez, {Keyla A.} and Pertile, {Kelly Kathleen} and Carolina Restrepo and Cardoso, {Barbara Rita} and Rembach, {Alan R.} and Roberts, {Blaine R.} and Robertson, {Joanne S.} and Rumble, {Rebecca L.} and Ryan, {Timothy M.} and Jack Sach and Silbert, {Brendan S.} and Christine Thai and Trounson, {Brett O.} and Irene Volitakis and Michael Vovos and Larry Ward and Watt, {Andrew D.} and Robert Williams and Woodward., {Michael Clifford} and Yates, {Paul A.} and Ugarte, {Fernanda Yevenes} and Ping Zhang and Bird, {Sabine M.} and Belinda Brown and Burnham, {Samantha C.} and Pratishtha Chatterjee and Cox, {Kay L.} and Shane Fernandez and Fernando, {Warnakulasuriya M.A.D.B.} and Gardener, {Samantha L.} and Laws, {Simon M.} and Florence Lim and Lucy Lim and Tegg, {Michelle L.} and Kathy Lucas and Georgia Martins and Tenielle Porter and Rainey-Smith, {Stephanie R.} and Rodrigues, {Mark A.} and Kaikai Shen and Sohrabi, {Hamid R.} and Kevin Taddei and Tania Taddei and Sherilyn Tan and Giuseppe Verdile and Michael Weinborn and Maree Farrow and Frost, {Shaun M.} and David Hanson and Maryam Hor and Yogesan Kanagasingam and Leifert, {Wayne Richard} and Lockett, {Linda Jane} and Malcolm Riley and Saunders, {Ian W.} and Philip Thomas",

note = "(CC-BY 4.0) Open Access article licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license (http://creativecommons.org/licenses/by/4.0) . ",

year = "2017",

month = oct,

day = "25",

doi = "10.1038/s41598-017-14020-9",

language = "English",

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journal = "Scientific Reports",

issn = "2045-2322",

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number = "1",

}

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TY - JOUR

T1 - A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort

AU - Pedrini, Steve

AU - Gupta, Veer Bala

AU - Hone, Eugene

AU - Doecke, James D.

AU - O'Bryant, Sid E.

AU - James, Ian R.

AU - Bush, Ashley I.

AU - Rowe, Christopher C.

AU - Villemagne, Victor L.

AU - Ames, David J.

AU - Masters, Colin L.

AU - Martins, Ralph N.

AU - AIBL Research Group

AU - Savage, Gregory R.

AU - Wilson, Bill

AU - Bourgeat, Pierrick T.

AU - Fripp, Jürgen

AU - Gibson, Simon

AU - Leroux, Hugo

AU - McBride, Simon J.

AU - Salvado, Olivier

AU - Fenech, Michael Felix

AU - François, Maxime

AU - Barnes, Mary B.

AU - Baker, Jenalle E.

AU - Barnham, Kevin Jeffrey

AU - Bellingham, Shayne A.

AU - Bomke, Julia

AU - Pejoska, Svetlana Bozin

AU - Buckley, Rachel F.

AU - Cheng, Lesley

AU - Collins, Steven John

AU - Cooke, Ian

AU - Cyarto, Elizabeth V.

AU - Darby, David G.

AU - Doré, Vincent

AU - El-Sheikh, Denise

AU - Faux, Noel G.

AU - Fowler, Christopher J.

AU - Harrington, Karra D.

AU - Hill, Andrew F.

AU - Horne, Malcolm Kenneth

AU - Jones, Gareth R.

AU - Kamer, Adrian

AU - Killeen, Neil

AU - Korrel, Hannah

AU - Lamb, Fiona

AU - Lautenschlager, Nicola T.

AU - Lennon, Kate

AU - Li, Qiaoxin

AU - Lim, Yen Ying

AU - Louey, Andrea G.

AU - Macaulay, Lance S.

AU - Mackintosh, Lucy

AU - Maruff, Paul T.

AU - McIlroy, Alissandra M.

AU - Nigro, Julie

AU - Perez, Keyla A.

AU - Pertile, Kelly Kathleen

AU - Restrepo, Carolina

AU - Cardoso, Barbara Rita

AU - Rembach, Alan R.

AU - Roberts, Blaine R.

AU - Robertson, Joanne S.

AU - Rumble, Rebecca L.

AU - Ryan, Timothy M.

AU - Sach, Jack

AU - Silbert, Brendan S.

AU - Thai, Christine

AU - Trounson, Brett O.

AU - Volitakis, Irene

AU - Vovos, Michael

AU - Ward, Larry

AU - Watt, Andrew D.

AU - Williams, Robert

AU - Woodward., Michael Clifford

AU - Yates, Paul A.

AU - Ugarte, Fernanda Yevenes

AU - Zhang, Ping

AU - Bird, Sabine M.

AU - Brown, Belinda

AU - Burnham, Samantha C.

AU - Chatterjee, Pratishtha

AU - Cox, Kay L.

AU - Fernandez, Shane

AU - Fernando, Warnakulasuriya M.A.D.B.

AU - Gardener, Samantha L.

AU - Laws, Simon M.

AU - Lim, Florence

AU - Lim, Lucy

AU - Tegg, Michelle L.

AU - Lucas, Kathy

AU - Martins, Georgia

AU - Porter, Tenielle

AU - Rainey-Smith, Stephanie R.

AU - Rodrigues, Mark A.

AU - Shen, Kaikai

AU - Sohrabi, Hamid R.

AU - Taddei, Kevin

AU - Taddei, Tania

AU - Tan, Sherilyn

AU - Verdile, Giuseppe

AU - Weinborn, Michael

AU - Farrow, Maree

AU - Frost, Shaun M.

AU - Hanson, David

AU - Hor, Maryam

AU - Kanagasingam, Yogesan

AU - Leifert, Wayne Richard

AU - Lockett, Linda Jane

AU - Riley, Malcolm

AU - Saunders, Ian W.

AU - Thomas, Philip

N1 - (CC-BY 4.0) Open Access article licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license (http://creativecommons.org/licenses/by/4.0) .

PY - 2017/10/25

Y1 - 2017/10/25

N2 - Alzheimer's Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer's participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ϵ4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ϵ4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.

AB - Alzheimer's Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer's participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ϵ4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ϵ4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.

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U2 - 10.1038/s41598-017-14020-9

DO - 10.1038/s41598-017-14020-9

M3 - Article

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 14057

ER -

A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort

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