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
Por:
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, Lleo, A, Peyratout, G, Tainta, M, Johannsen, P, Freund-Levi, Y, Frolich, 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
Publicada:
1 jun 2019
Resumen:
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/).
Filiaciones:
Kim, M:
Kings Coll London, Inst Pharmaceut Sci, London, England
Steno Diabet Ctr Copenhagen, Gentofte, Denmark
Snowden, S:
Kings Coll London, Inst Pharmaceut Sci, London, England
Univ Cambridge, Inst Metab Sci, Cambridge, England
Suvitaival, T:
Steno Diabet Ctr Copenhagen, Gentofte, Denmark
Ali, A:
Steno Diabet Ctr Copenhagen, Gentofte, Denmark
Ahmad, T:
Kings Coll London, Inst Pharmaceut Sci, London, England
Westwood, S:
Univ Oxford, Dept Psychiat, Oxford, England
Baird, A:
Univ Oxford, Dept Psychiat, Oxford, England
Proitsi, P:
Kings Coll London, Maurice Wohl Clin Neurosci Inst, Inst Psychiat Psychol & Neurosci, London, England
Nevado-Holgado, A:
Univ Oxford, Dept Psychiat, Oxford, England
Hye, A:
Steno Diabet Ctr Copenhagen, Gentofte, Denmark
Bos, I:
Maastricht Univ, Alzheimer Ctr Limburg, Maastricht, Netherlands
Vos, S:
Maastricht Univ, Alzheimer Ctr Limburg, Maastricht, Netherlands
Vandenberghe, R:
Univ Hosp Leuven, Leuven, Belgium
Teunissen, C:
Univ Amsterdam, Med Ctr, Neurochem Lab, Dept Clin Chem,Amsterdam Neurosci, Amsterdam, Netherlands
Univ Amsterdam, Med Ctr, Biobank, Dept Clin Chem,Amsterdam Neurosci, Amsterdam, Netherlands
ten Kate, M:
Univ Amsterdam, Med Ctr, Neurochem Lab, Dept Clin Chem,Amsterdam Neurosci, Amsterdam, Netherlands
Univ Amsterdam, Med Ctr, Biobank, Dept Clin Chem,Amsterdam Neurosci, Amsterdam, Netherlands
Scheltens, P:
Univ Amsterdam, Med Ctr, Alzheimer Ctr, Dept Neurol, Amsterdam, Netherlands
Gabel, S:
Univ Hosp Leuven, Leuven, Belgium
Katholieke Univ Leuven, Dept Neurosci, Lab Cognit Neurol, Leuven, Belgium
Meersmans, K:
Univ Hosp Leuven, Leuven, Belgium
Katholieke Univ Leuven, Dept Neurosci, Lab Cognit Neurol, Leuven, Belgium
Blin, O:
Aix Marseille Univ, Serv Pharmacol Clin & Pharmacovigilance, Inst Neurosci Syst, APHM,INSERM, Marseille, France
Richardson, J:
GlaxoSmithKline R&D, Neurosci Therapeut Area, Stevenage, Herts, England
De Roeck, E:
Univ Antwerp, Inst Born Bunge, Antwerp, Belgium
Sleegers, K:
Univ Antwerp, Inst Born Bunge, Antwerp, Belgium
VIB, Ctr Mol Neurol, Neurodegenerat Brain Dis Grp, Flanders, Belgium
Bordet, R:
Univ Lille, INSERM, CHU, Degenerat & Vasc Cognit Disorders, Lille, France
Rami, L:
Hosp Clin IDIBAPS, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Kettunen, P:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden
Sahlgrens Univ Hosp, Dept Neuropsychiat, Memory Clin, Gothenburg, Sweden
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, West Wing, Oxford, England
Tsolaki, M:
AHEPA Univ Hosp, Dept Neurol 1, Thessaloniki, Greece
Verhey, F:
Maastricht Univ, Alzheimer Ctr Limburg, Maastricht, Netherlands
Sala, I:
Hosp Santa Creu & Sant Pau, Neurol Dept, Memory Unit, Barcelona, Spain
Lleo, A:
Hosp Santa Creu & Sant Pau, Neurol Dept, Memory Unit, Barcelona, Spain
Peyratout, G:
Univ Hosp Lausanne, Lausanne, Switzerland
Tainta, M:
CITA Alzheimer Fdn, San Sebastian, Spain
Johannsen, P:
Copenhagen Univ Hosp, Danish Dementia Res Ctr, Rigshosp, Copenhagen, Denmark
Freund-Levi, Y:
Karolinska Inst, Div Clin Geriatr, Dept Neurobiol Caring Sci & Soc NVS, Stockholm, Sweden
Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden
Frolich, L:
Heidelberg Univ, Dept Geriatr Psychiat, Zent Inst Seel Gesundheit, Mannheim, Germany
Dobricic, V:
Univ Cambridge, Dept Biochem, Cambridge, England
Lubeck Interdisciplinary Platform Genome Analyt, Lubeck, Germany
Engelborghs, S:
Univ S Florida, Dept Chem, Tampa, FL 33620 USA
Univ Antwerp, Inst Born Bunge, Antwerp, Belgium
Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Dept Neurol, Antwerp, Belgium
Hosp Network Antwerp ZNA Middelheim & Hoge Beuken, Memory Clin, Antwerp, Belgium
Frisoni, GB:
Univ Geneva, Geneva, Switzerland
Molinuevo, JL:
Hosp Clin IDIBAPS, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Pasqual Maragall Fdn, Barcelona Beta Brain Res Ctr, Barcelona, Spain
Wallin, A:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden
Popp, J:
Univ Hosp Lausanne, Lausanne, Switzerland
Geneva Univ Hosp, Dept Mental Hlth & Psychiat, Geriatr Psychiat, Geneva, Switzerland
Martinez-Lage, P:
CITA Alzheimer Fdn, San Sebastian, Spain
Bertram, L:
Univ Lubeck, Lubeck, Germany
Barkhof, F:
Univ Amsterdam, Med Ctr, Neurochem Lab, Dept Clin Chem,Amsterdam Neurosci, Amsterdam, Netherlands
Univ Amsterdam, Med Ctr, Biobank, Dept Clin Chem,Amsterdam Neurosci, Amsterdam, Netherlands
Ashton, N:
Steno Diabet Ctr Copenhagen, Gentofte, Denmark
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden
Blennow, K:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
UCL Inst Neurol, Dept Mol Neurosci, London, England
UCL, UK Dementia Res Inst, London, England
Streffer, J:
Janssen Pharmaceut Co, Expt Med, Beerse, Belgium
Visser, PJ:
Maastricht Univ, Alzheimer Ctr Limburg, Maastricht, Netherlands
Univ Amsterdam, Med Ctr, Neurochem Lab, Dept Clin Chem,Amsterdam Neurosci, Amsterdam, Netherlands
Univ Amsterdam, Med Ctr, Biobank, Dept Clin Chem,Amsterdam Neurosci, Amsterdam, Netherlands
Lovestone, S:
Univ Oxford, Dept Psychiat, Oxford, England
Legido-Quigley, C:
Kings Coll London, Inst Pharmaceut Sci, London, England
Steno Diabet Ctr Copenhagen, Gentofte, Denmark
Green Published, Green Accepted, Hybrid Gold
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