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 - http://www.scopus.com/inward/record.url?scp=85066602218&partnerID=8YFLogxK
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 -
