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 B. Gupta; Eugene Hone; James Doecke; Sid O'Bryant; Ian James; Ashley I. Bush; Christopher C. Rowe; Victor L. Villemagne; David Ames; Colin L. Masters; Ralph N. Martins; Greg Savage; Bill Wilson; Pierrick Bourgeat; Jurgen Fripp; Simon Gibson; Hugo Leroux; Simon McBride; Olivier Salvado; Michael Fenech; Maxime Francois; Mary Barnes; Jenalle Baker; Kevin Barnham; Shayne Bellingham; Julia Bomke; Sveltana Bozin Pejoska; Rachel Buckley; Lesley Cheng; Steven Collins; Ian Cooke; Elizabeth Cyarto; David Darby; Vincent Dore; Denise El-Sheikh; Noel Faux; Christopher Fowler; Karra Harrington; Andy Hill; Malcolm Horne; Gareth Jones; Adrian Kamer; Neil Killeen; Hannah Korrel; Fiona Lamb; Nicola Lautenschlager; Kate Lennon; Qiao Xin Li; Yen Ying Lim; Andrea Louey; Lance Macaulay; Lucy Mackintosh; Paul Maruff; Alissandra McIlroy; Julie Nigro; Kayla Perez; Kelly Pertile; Carolina Restrepo; Barbara Rita Cardoso; Alan Rembach; Blaine Roberts; Jo Robertson; Rebecca Rumble; Tim Ryan; Jack Sach; Brendan Silbert; Christine Thai; Brett Trounson; Irene Volitakis; Michael Vovos; Larry Ward; Andrew Watt; Rob Williams; Michael Woodward; Paul Yates; Fernanda Yevenes Ugarte; Ping Zhang; Sabine Bird; Belinda Brown; Samantha Burnham; Pratishtha Chatterjee; Kay Cox; Shane Fernandez; Binosha Fernando; Sam Gardener; Simon Laws; Florence Lim; Lucy Lim; Michelle Tegg; Kathy Lucas; Georgia Martins; Tenielle Porter; Stephanie Rainey-Smith; Mark Rodrigues; Kaikai Shen; Harmid Sohrabi; Kevin Taddei; Tania Taddei; Sherilyn Tan; Giuseppe Verdile; Mike Weinborn; Maree Farrow; Shaun Frost; David Hanson; Maryam Hor; Yogi Kanagasingam; Wayne Leifert; Linda Lockett; Malcolm Riley; Ian 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 B. Gupta, Eugene Hone, James Doecke, Sid O'Bryant, Ian James, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Ralph N. Martins, Greg Savage, Bill Wilson, Pierrick Bourgeat, Jurgen Fripp, Simon Gibson, Hugo Leroux, Simon McBride, Olivier SalvadoMichael Fenech, Maxime Francois, Mary Barnes, Jenalle Baker, Kevin Barnham, Shayne Bellingham, Julia Bomke, Sveltana Bozin Pejoska, Rachel Buckley, Lesley Cheng, Steven Collins, Ian Cooke, Elizabeth Cyarto, David Darby, Vincent Dore, Denise El-Sheikh, Noel Faux, Christopher Fowler, Karra Harrington, Andy Hill, Malcolm Horne, Gareth Jones, Adrian Kamer, Neil Killeen, Hannah Korrel, Fiona Lamb, Nicola Lautenschlager, Kate Lennon, Qiao Xin Li, Yen Ying Lim, Andrea Louey, Lance Macaulay, Lucy Mackintosh, Paul Maruff, Alissandra McIlroy, Julie Nigro, Kayla Perez, Kelly Pertile, Carolina Restrepo, Barbara Rita Cardoso, Alan Rembach, Blaine Roberts, Jo Robertson, Rebecca Rumble, Tim Ryan, Jack Sach, Brendan Silbert, Christine Thai, Brett Trounson, Irene Volitakis, Michael Vovos, Larry Ward, Andrew Watt, Rob Williams, Michael Woodward, Paul Yates, Fernanda Yevenes Ugarte, Ping Zhang, Sabine Bird, Belinda Brown, Samantha Burnham, Pratishtha Chatterjee, Kay Cox, Shane Fernandez, Binosha Fernando, Sam Gardener, Simon Laws, Florence Lim, Lucy Lim, Michelle Tegg, Kathy Lucas, Georgia Martins, Tenielle Porter, Stephanie Rainey-Smith, Mark Rodrigues, Kaikai Shen, Harmid Sohrabi, Kevin Taddei, Tania Taddei, Sherilyn Tan, Giuseppe Verdile, Mike Weinborn, Maree Farrow, Shaun Frost, David Hanson, Maryam Hor, Yogi Kanagasingam, Wayne Leifert, Linda Lockett, Malcolm Riley, Ian 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
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-14020-9
State	Published - 1 Dec 2017

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Pedrini, S., Gupta, V. B., Hone, E., Doecke, J., O'Bryant, S., James, I., Bush, A. I., Rowe, C. C., Villemagne, V. L., Ames, D., Masters, C. L., Martins, R. N., Savage, G., Wilson, B., Bourgeat, P., Fripp, J., Gibson, S., Leroux, H., McBride, S., ... 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), [14057]. https://doi.org/10.1038/s41598-017-14020-9

@article{7406bbc639814ad49e4e1fc46a640a1e,

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 B.} and Eugene Hone and James Doecke and Sid O'Bryant and Ian James and Bush, {Ashley I.} and Rowe, {Christopher C.} and Villemagne, {Victor L.} and David Ames and Masters, {Colin L.} and Martins, {Ralph N.} and Greg Savage and Bill Wilson and Pierrick Bourgeat and Jurgen Fripp and Simon Gibson and Hugo Leroux and Simon McBride and Olivier Salvado and Michael Fenech and Maxime Francois and Mary Barnes and Jenalle Baker and Kevin Barnham and Shayne Bellingham and Julia Bomke and Pejoska, {Sveltana Bozin} and Rachel Buckley and Lesley Cheng and Steven Collins and Ian Cooke and Elizabeth Cyarto and David Darby and Vincent Dore and Denise El-Sheikh and Noel Faux and Christopher Fowler and Karra Harrington and Andy Hill and Malcolm Horne and Gareth Jones and Adrian Kamer and Neil Killeen and Hannah Korrel and Fiona Lamb and Nicola Lautenschlager and Kate Lennon and Li, {Qiao Xin} and Lim, {Yen Ying} and Andrea Louey and Lance Macaulay and Lucy Mackintosh and Paul Maruff and Alissandra McIlroy and Julie Nigro and Kayla Perez and Kelly Pertile and Carolina Restrepo and Cardoso, {Barbara Rita} and Alan Rembach and Blaine Roberts and Jo Robertson and Rebecca Rumble and Tim Ryan and Jack Sach and Brendan Silbert and Christine Thai and Brett Trounson and Irene Volitakis and Michael Vovos and Larry Ward and Andrew Watt and Rob Williams and Michael Woodward and Paul Yates and Ugarte, {Fernanda Yevenes} and Ping Zhang and Sabine Bird and Belinda Brown and Samantha Burnham and Pratishtha Chatterjee and Kay Cox and Shane Fernandez and Binosha Fernando and Sam Gardener and Simon Laws and Florence Lim and Lucy Lim and Michelle Tegg and Kathy Lucas and Georgia Martins and Tenielle Porter and Stephanie Rainey-Smith and Mark Rodrigues and Kaikai Shen and Harmid Sohrabi and Kevin Taddei and Tania Taddei and Sherilyn Tan and Giuseppe Verdile and Mike Weinborn and Maree Farrow and Shaun Frost and David Hanson and Maryam Hor and Yogi Kanagasingam and Wayne Leifert and Linda Lockett and Malcolm Riley and Ian Saunders and Philip Thomas",

note = "Funding Information: Competing Interests: S. O{\textquoteright}Bryant has received honorarium for involvement in Roche Diagnostics Advisory Board and has multiple patents pending regarding blood-based biomarkers in neurodegenerative diseases. He is supported by funds from the NIH/NIA (AG051848). Funding Information: We thank all the participants who took part in this study and the clinicians who referred participants. The AIBL study (www.AIBL.csiro.au) is a collaboration between CSIRO, Edith Cowan University (ECU), National Ageing Research Institute (NARI), The Florey Institute of Neuroscience and Mental Health (FINMH) and Austin Health. It also received support from Hollywood Private Hospital, CogState Ltd., and Sir Charles Gairdner Hospital and funding support from Alzheimer{\textquoteright}s Australia (AA), CSIRO, the Science and Industry Endowment Fund, McCusker Alzheimer{\textquoteright}s Research Foundation, Brightfocus, USA and the WA Dept. of Health, as well as industry sources. The authors acknowledge the financial support of the Cooperative Research Centre (CRC) for Mental Health, which is an Australian Government Initiative. Pfizer International has provided financial support to assist with analysis of blood samples and to further the AIBL research program. Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

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

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Pedrini, S, Gupta, VB, Hone, E, Doecke, J, O'Bryant, S, James, I, Bush, AI, Rowe, CC, Villemagne, VL, Ames, D, Masters, CL, Martins, RN, Savage, G, Wilson, B, Bourgeat, P, Fripp, J, Gibson, S, Leroux, H, McBride, S, Salvado, O, Fenech, M, Francois, M, Barnes, M, Baker, J, Barnham, K, Bellingham, S, Bomke, J, Pejoska, SB, Buckley, R, Cheng, L, Collins, S, Cooke, I, Cyarto, E, Darby, D, Dore, V, El-Sheikh, D, Faux, N, Fowler, C, Harrington, K, Hill, A, Horne, M, Jones, G, Kamer, A, Killeen, N, Korrel, H, Lamb, F, Lautenschlager, N, Lennon, K, Li, QX, Lim, YY, Louey, A, Macaulay, L, Mackintosh, L, Maruff, P, McIlroy, A, Nigro, J, Perez, K, Pertile, K, Restrepo, C, Cardoso, BR, Rembach, A, Roberts, B, Robertson, J, Rumble, R, Ryan, T, Sach, J, Silbert, B, Thai, C, Trounson, B, Volitakis, I, Vovos, M, Ward, L, Watt, A, Williams, R, Woodward, M, Yates, P, Ugarte, FY, Zhang, P, Bird, S, Brown, B, Burnham, S, Chatterjee, P, Cox, K, Fernandez, S, Fernando, B, Gardener, S, Laws, S, Lim, F, Lim, L, Tegg, M, Lucas, K, Martins, G, Porter, T, Rainey-Smith, S, Rodrigues, M, Shen, K, Sohrabi, H, Taddei, K, Taddei, T, Tan, S, Verdile, G, Weinborn, M, Farrow, M, Frost, S, Hanson, D, Hor, M, Kanagasingam, Y, Leifert, W, Lockett, L, Riley, M, Saunders, I & 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, vol. 7, no. 1, 14057. https://doi.org/10.1038/s41598-017-14020-9

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 B.

AU - Hone, Eugene

AU - Doecke, James

AU - O'Bryant, Sid

AU - James, Ian

AU - Bush, Ashley I.

AU - Rowe, Christopher C.

AU - Villemagne, Victor L.

AU - Ames, David

AU - Masters, Colin L.

AU - Martins, Ralph N.

AU - Savage, Greg

AU - Wilson, Bill

AU - Bourgeat, Pierrick

AU - Fripp, Jurgen

AU - Gibson, Simon

AU - Leroux, Hugo

AU - McBride, Simon

AU - Salvado, Olivier

AU - Fenech, Michael

AU - Francois, Maxime

AU - Barnes, Mary

AU - Baker, Jenalle

AU - Barnham, Kevin

AU - Bellingham, Shayne

AU - Bomke, Julia

AU - Pejoska, Sveltana Bozin

AU - Buckley, Rachel

AU - Cheng, Lesley

AU - Collins, Steven

AU - Cooke, Ian

AU - Cyarto, Elizabeth

AU - Darby, David

AU - Dore, Vincent

AU - El-Sheikh, Denise

AU - Faux, Noel

AU - Fowler, Christopher

AU - Harrington, Karra

AU - Hill, Andy

AU - Horne, Malcolm

AU - Jones, Gareth

AU - Kamer, Adrian

AU - Killeen, Neil

AU - Korrel, Hannah

AU - Lamb, Fiona

AU - Lautenschlager, Nicola

AU - Lennon, Kate

AU - Li, Qiao Xin

AU - Lim, Yen Ying

AU - Louey, Andrea

AU - Macaulay, Lance

AU - Mackintosh, Lucy

AU - Maruff, Paul

AU - McIlroy, Alissandra

AU - Nigro, Julie

AU - Perez, Kayla

AU - Pertile, Kelly

AU - Restrepo, Carolina

AU - Cardoso, Barbara Rita

AU - Rembach, Alan

AU - Roberts, Blaine

AU - Robertson, Jo

AU - Rumble, Rebecca

AU - Ryan, Tim

AU - Sach, Jack

AU - Silbert, Brendan

AU - Thai, Christine

AU - Trounson, Brett

AU - Volitakis, Irene

AU - Vovos, Michael

AU - Ward, Larry

AU - Watt, Andrew

AU - Williams, Rob

AU - Woodward, Michael

AU - Yates, Paul

AU - Ugarte, Fernanda Yevenes

AU - Zhang, Ping

AU - Bird, Sabine

AU - Brown, Belinda

AU - Burnham, Samantha

AU - Chatterjee, Pratishtha

AU - Cox, Kay

AU - Fernandez, Shane

AU - Fernando, Binosha

AU - Gardener, Sam

AU - Laws, Simon

AU - Lim, Florence

AU - Lim, Lucy

AU - Tegg, Michelle

AU - Lucas, Kathy

AU - Martins, Georgia

AU - Porter, Tenielle

AU - Rainey-Smith, Stephanie

AU - Rodrigues, Mark

AU - Shen, Kaikai

AU - Sohrabi, Harmid

AU - Taddei, Kevin

AU - Taddei, Tania

AU - Tan, Sherilyn

AU - Verdile, Giuseppe

AU - Weinborn, Mike

AU - Farrow, Maree

AU - Frost, Shaun

AU - Hanson, David

AU - Hor, Maryam

AU - Kanagasingam, Yogi

AU - Leifert, Wayne

AU - Lockett, Linda

AU - Riley, Malcolm

AU - Saunders, Ian

AU - Thomas, Philip

N1 - Funding Information: Competing Interests: S. O’Bryant has received honorarium for involvement in Roche Diagnostics Advisory Board and has multiple patents pending regarding blood-based biomarkers in neurodegenerative diseases. He is supported by funds from the NIH/NIA (AG051848). Funding Information: We thank all the participants who took part in this study and the clinicians who referred participants. The AIBL study (www.AIBL.csiro.au) is a collaboration between CSIRO, Edith Cowan University (ECU), National Ageing Research Institute (NARI), The Florey Institute of Neuroscience and Mental Health (FINMH) and Austin Health. It also received support from Hollywood Private Hospital, CogState Ltd., and Sir Charles Gairdner Hospital and funding support from Alzheimer’s Australia (AA), CSIRO, the Science and Industry Endowment Fund, McCusker Alzheimer’s Research Foundation, Brightfocus, USA and the WA Dept. of Health, as well as industry sources. The authors acknowledge the financial support of the Cooperative Research Centre (CRC) for Mental Health, which is an Australian Government Initiative. Pfizer International has provided financial support to assist with analysis of blood samples and to further the AIBL research program. Publisher Copyright: © 2017 The Author(s).

PY - 2017/12/1

Y1 - 2017/12/1

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

C2 - 29070909

AN - SCOPUS:85032174892

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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