Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort

Min Kim; Stuart Snowden; Tommi Suvitaival; Ashfaq Ali; David J. Merkler; Tahmina Ahmad; Sarah Westwood; Alison Baird; Petroula Proitsi; Alejo Nevado-Holgado; Abdul Hye; Isabelle Bos; Stephanie Vos; Rik Vandenberghe; Charlotte Teunissen; Mara ten Kate; Philip Scheltens; Silvy Gabel; Karen Meersmans; Olivier Blin; Jill Richardson; Ellen De Roeck; Kristel Sleegers; Régis Bordet; Lorena Rami; Petronella Kettunen; Magda Tsolaki; Frans Verhey; Isabel Sala; Alberto Lléo; Gwendoline Peyratout; Mikel Tainta; Peter Johannsen; Yvonne Freund-Levi; Lutz Frölich; Valerija Dobricic; Sebastiaan Engelborghs; Giovanni B. Frisoni; José L. Molinuevo; Anders Wallin; Julius Popp; Pablo Martinez-Lage; Lars Bertram; Frederik Barkhof; Nicholas Ashton; Kaj Blennow; Henrik Zetterberg; Johannes Streffer; Pieter J. Visser; Simon Lovestone; Cristina Legido-Quigley

doi:10.1016/j.jalz.2019.03.004

Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort

Min Kim, Stuart Snowden, Tommi Suvitaival, Ashfaq Ali, David J. Merkler, Tahmina Ahmad, Sarah Westwood, Alison Baird, Petroula Proitsi, Alejo Nevado-Holgado, Abdul Hye, Isabelle Bos, Stephanie Vos, Rik Vandenberghe, Charlotte Teunissen, Mara ten Kate, Philip Scheltens, Silvy Gabel, Karen Meersmans, Olivier BlinJill Richardson, Ellen De Roeck, Kristel Sleegers, Régis Bordet, Lorena Rami, Petronella Kettunen, Magda Tsolaki, Frans Verhey, Isabel Sala, Alberto Lléo, Gwendoline Peyratout, Mikel Tainta, Peter Johannsen, Yvonne Freund-Levi, Lutz Frölich, Valerija Dobricic, Sebastiaan Engelborghs, Giovanni B. Frisoni, José L. Molinuevo, Anders Wallin, Julius Popp, Pablo Martinez-Lage, Lars Bertram, Frederik Barkhof, Nicholas Ashton, Kaj Blennow, Henrik Zetterberg, Johannes Streffer, Pieter J. Visser, Simon Lovestone, Cristina Legido-Quigley^*

^*Corresponding author for this work

Institute of Neurogenetics

69 Citations (Scopus)

Abstract

Introduction: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers. Methods: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis. Results: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory. Discussion: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.

Original language	English
Journal	Alzheimer's and Dementia
Volume	15
Issue number	6
Pages (from-to)	817-827
Number of pages	11
ISSN	1552-5260
DOIs	https://doi.org/10.1016/j.jalz.2019.03.004
Publication status	Published - 06.2019

Funding

Funding: The present study was conducted as part of the EMIF-AD project, which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and EFPIA companies' in-kind contribution. The DESCRIPA study was funded by the European Commission within the fifth framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission within the fifth framework program (contract no. 37670). The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). D.J.M was partially supported by a grant from the National Institutes of Health ( R15-GM107864 ).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Research Area: Medical Genetics

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10.1016/j.jalz.2019.03.004

Cite this

Kim, M., Snowden, S., Suvitaival, T., Ali, A., Merkler, D. J., Ahmad, T., Westwood, S., Baird, A., Proitsi, P., Nevado-Holgado, A., Hye, A., Bos, I., Vos, S., Vandenberghe, R., Teunissen, C., ten Kate, M., Scheltens, P., Gabel, S., Meersmans, K., ... Legido-Quigley, C. (2019). Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort. Alzheimer's and Dementia, 15(6), 817-827. https://doi.org/10.1016/j.jalz.2019.03.004

@article{960a91baaffc4951894ae735f89d7b5d,

title = "Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort",

abstract = "Introduction: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers. Methods: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis. Results: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory. Discussion: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.",

author = "Min Kim and Stuart Snowden and Tommi Suvitaival and Ashfaq Ali and Merkler, \{David J.\} and Tahmina Ahmad and Sarah Westwood and Alison Baird and Petroula Proitsi and Alejo Nevado-Holgado and Abdul Hye and Isabelle Bos and Stephanie Vos and Rik Vandenberghe and Charlotte Teunissen and \{ten Kate\}, Mara and Philip Scheltens and Silvy Gabel and Karen Meersmans and Olivier Blin and Jill Richardson and \{De Roeck\}, Ellen and Kristel Sleegers and R{\'e}gis Bordet and Lorena Rami and Petronella Kettunen and Magda Tsolaki and Frans Verhey and Isabel Sala and Alberto Ll{\'e}o and Gwendoline Peyratout and Mikel Tainta and Peter Johannsen and Yvonne Freund-Levi and Lutz Fr{\"o}lich and Valerija Dobricic and Sebastiaan Engelborghs and Frisoni, \{Giovanni B.\} and Molinuevo, \{Jos{\'e} L.\} and Anders Wallin and Julius Popp and Pablo Martinez-Lage and Lars Bertram and Frederik Barkhof and Nicholas Ashton and Kaj Blennow and Henrik Zetterberg and Johannes Streffer and Visser, \{Pieter J.\} and Simon Lovestone and Cristina Legido-Quigley",

note = "Funding Information: Funding: The present study was conducted as part of the EMIF-AD project, which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and EFPIA companies' in-kind contribution. The DESCRIPA study was funded by the European Commission within the fifth framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission within the fifth framework program (contract no. 37670). The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). Funding Information: D.J.M was partially supported by a grant from the National Institutes of Health ( R15-GM107864 ). Publisher Copyright: {\textcopyright} 2019 Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

month = jun,

doi = "10.1016/j.jalz.2019.03.004",

language = "English",

volume = "15",

pages = "817--827",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc",

number = "6",

}

Kim, M, Snowden, S, Suvitaival, T, Ali, A, Merkler, DJ, Ahmad, T, Westwood, S, Baird, A, Proitsi, P, Nevado-Holgado, A, Hye, A, Bos, I, Vos, S, Vandenberghe, R, Teunissen, C, ten Kate, M, Scheltens, P, Gabel, S, Meersmans, K, Blin, O, Richardson, J, De Roeck, E, Sleegers, K, Bordet, R, Rami, L, Kettunen, P, Tsolaki, M, Verhey, F, Sala, I, Lléo, A, Peyratout, G, Tainta, M, Johannsen, P, Freund-Levi, Y, Frölich, L, Dobricic, V, Engelborghs, S, Frisoni, GB, Molinuevo, JL, Wallin, A, Popp, J, Martinez-Lage, P, Bertram, L, Barkhof, F, Ashton, N, Blennow, K, Zetterberg, H, Streffer, J, Visser, PJ, Lovestone, S & Legido-Quigley, C 2019, 'Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort', Alzheimer's and Dementia, vol. 15, no. 6, pp. 817-827. https://doi.org/10.1016/j.jalz.2019.03.004

Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort. / Kim, Min; Snowden, Stuart; Suvitaival, Tommi et al.
In: Alzheimer's and Dementia, Vol. 15, No. 6, 06.2019, p. 817-827.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort

AU - Kim, Min

AU - Snowden, Stuart

AU - Suvitaival, Tommi

AU - Ali, Ashfaq

AU - Merkler, David J.

AU - Ahmad, Tahmina

AU - Westwood, Sarah

AU - Baird, Alison

AU - Proitsi, Petroula

AU - Nevado-Holgado, Alejo

AU - Hye, Abdul

AU - Bos, Isabelle

AU - Vos, Stephanie

AU - Vandenberghe, Rik

AU - Teunissen, Charlotte

AU - ten Kate, Mara

AU - Scheltens, Philip

AU - Gabel, Silvy

AU - Meersmans, Karen

AU - Blin, Olivier

AU - Richardson, Jill

AU - De Roeck, Ellen

AU - Sleegers, Kristel

AU - Bordet, Régis

AU - Rami, Lorena

AU - Kettunen, Petronella

AU - Tsolaki, Magda

AU - Verhey, Frans

AU - Sala, Isabel

AU - Lléo, Alberto

AU - Peyratout, Gwendoline

AU - Tainta, Mikel

AU - Johannsen, Peter

AU - Freund-Levi, Yvonne

AU - Frölich, Lutz

AU - Dobricic, Valerija

AU - Engelborghs, Sebastiaan

AU - Frisoni, Giovanni B.

AU - Molinuevo, José L.

AU - Wallin, Anders

AU - Popp, Julius

AU - Martinez-Lage, Pablo

AU - Bertram, Lars

AU - Barkhof, Frederik

AU - Ashton, Nicholas

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Streffer, Johannes

AU - Visser, Pieter J.

AU - Lovestone, Simon

AU - Legido-Quigley, Cristina

N1 - Funding Information: Funding: The present study was conducted as part of the EMIF-AD project, which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and EFPIA companies' in-kind contribution. The DESCRIPA study was funded by the European Commission within the fifth framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission within the fifth framework program (contract no. 37670). The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). Funding Information: D.J.M was partially supported by a grant from the National Institutes of Health ( R15-GM107864 ). Publisher Copyright: © 2019 Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/6

Y1 - 2019/6

N2 - Introduction: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers. Methods: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis. Results: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory. Discussion: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.

AB - Introduction: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers. Methods: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis. Results: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory. Discussion: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.

UR - https://www.scopus.com/pages/publications/85066602218

U2 - 10.1016/j.jalz.2019.03.004

DO - 10.1016/j.jalz.2019.03.004

M3 - Journal articles

C2 - 31078433

AN - SCOPUS:85066602218

SN - 1552-5260

VL - 15

SP - 817

EP - 827

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 6

ER -

Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort

Abstract

Funding

UN SDGs

Research Areas and Centers

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