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, Regis
AU - Rami, Lorena
AU - Kettunen, Petronella
AU - Tsolaki, Magda
AU - Verhey, Frans
AU - Sala, Isabel
AU - Lleo, Alberto
AU - Peyratout, Gwendoline
AU - Tainta, Mikel
AU - Johannsen, Peter
AU - Freund-Levi, Yvonne
AU - Frolich, Lutz
AU - Dobricic, Valerija
AU - Engelborghs, Sebastiaan
AU - Frisoni, Giovanni B.
AU - Molinuevo, Jose 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:
Conflict of interest: S.E. reports research funding from Janssen Pharmaceutica N.V. and ADx Neurosciences (paid to institution). A.N.-H. holds a funding award from Ono Pharmaceutical Co Ltd. L.F. has participated in advisory boards for Allergan, Eli Lilly, Avraham Pharmaceuticals, Axon Neuroscience, Axovant, Biogen, Boehringer Ingelheim, Eisai, Functional Neuromodulation, Lundbeck, MerckSharpe & Dohme, Novartis, Pfizer, Pharnext, Roche, Schwabe and has received research grants from Novartis. H.Z. has served at advisory boards for Eli Lilly, Roche Diagnostics, Wave, Samumed and CogRx, has received travel support from Teva, and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg (all unrelated to this study). F.B. has served at advisory boards for Bayer-Schering Pharma, Biogen, Teva, Merck-Serono, Novartis, Roche, Jansen Research, Genzyme-Sanofi, IXICO, GeNeuro, Apitope. All other authors report no biomedical financial interests or potential conflicts of interest.The authors thank the individuals and families who took part in this research. The authors would also like to thank all people involved in data and sample collection and/or logistics across the different centers, and in particular Marije Benedictus, Wiesje van de Flier, Charlotte Teunissen, Ellen De Roeck, Naomi De Roeck, Ellis Niemantsverdriet, Charisse Somers, Babette Reijs, Andrea Izagirre Otaegi, Mirian, Ecay Torres, Sindre Rolstad, Eva Bringman, Domilé Tautvydaité, Barbara Moullet, Charlotte Evenepoel, Isabelle Cleynen, Bea Bosch, Daniel Alcolea Rodriguez, Moira Marizzoni, Alberto Redolfi, and Paolo Bosco. 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).
Funding Information:
D.J.M was partially supported by a grant from the National Institutes of Health ( R15-GM107864 ).
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).
Publisher Copyright:
© 2019
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 b 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 b burden in CSF and clinical measures. Crown Copyright (C) 2019 Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
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 b 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 b burden in CSF and clinical measures. Crown Copyright (C) 2019 Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
KW - 12,13-DIHOME
KW - ACID
KW - Alzheimer's disease
KW - Amyloid
KW - BIOSYNTHESIS
KW - Biomarkers
KW - Brain volume measurements
KW - CSF
KW - Cognitive function measurements
KW - Dementia
KW - EMIF-AD
KW - INDUCED LIPOKINE
KW - MARKERS
KW - METABOLISM
KW - METABOLOMICS
KW - Metabolomics
KW - OLEAMIDE
KW - PERTURBATIONS
KW - RECOMMENDATIONS
KW - Tau
U2 - 10.1016/j.jalz.2019.03.004
DO - 10.1016/j.jalz.2019.03.004
M3 - Article
C2 - 31078433
SN - 1552-5260
VL - 15
SP - 817
EP - 827
JO - Alzheimer's & Dementia
JF - Alzheimer's & Dementia
IS - 6
ER -