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.


Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978

Informations de publication

Date de publication:
06 2019
Historique:
received: 08 08 2018
revised: 06 02 2019
accepted: 04 03 2019
pubmed: 13 5 2019
medline: 23 6 2020
entrez: 13 5 2019
Statut: ppublish

Résumé

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. 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. 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. PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.

Identifiants

pubmed: 31078433
pii: S1552-5260(19)30074-3
doi: 10.1016/j.jalz.2019.03.004
pmc: PMC6849698
mid: NIHMS1053807
pii:
doi:

Substances chimiques

Amyloid beta-Peptides 0
Biomarkers 0
tau Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

817-827

Subventions

Organisme : Medical Research Council
ID : MC_PC_17215
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R15 GM107864
Pays : United States

Informations de copyright

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

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Auteurs

Min Kim (M)

Institute of Pharmaceutical Science, King's College London, London, UK; Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Stuart Snowden (S)

Institute of Pharmaceutical Science, King's College London, London, UK; Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Biochemistry, University of Cambridge, Cambridge, UK.

Tommi Suvitaival (T)

Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Ashfaq Ali (A)

Steno Diabetes Center Copenhagen, Gentofte, Denmark.

David J Merkler (DJ)

Department of Chemistry, University of South Florida, Tampa, FL, USA.

Tahmina Ahmad (T)

Institute of Pharmaceutical Science, King's College London, London, UK.

Sarah Westwood (S)

Department of Psychiatry, University of Oxford, Oxford, UK.

Alison Baird (A)

Department of Psychiatry, University of Oxford, Oxford, UK.

Petroula Proitsi (P)

Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.

Alejo Nevado-Holgado (A)

Department of Psychiatry, University of Oxford, Oxford, UK.

Abdul Hye (A)

Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Isabelle Bos (I)

Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands.

Stephanie Vos (S)

Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands.

Rik Vandenberghe (R)

University Hospital Leuven, Leuven, Belgium.

Charlotte Teunissen (C)

Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam University Medical Centers, Amsterdam Neuroscience, Amsterdam, The Netherlands.

Mara Ten Kate (M)

Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam University Medical Centers, Amsterdam Neuroscience, Amsterdam, The Netherlands.

Philip Scheltens (P)

Department of Neurology, Alzheimer Center, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

Silvy Gabel (S)

University Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.

Karen Meersmans (K)

University Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.

Olivier Blin (O)

Service de Pharmacologie Clinique et Pharmacovigilance, Institut de Neurosciences des Systèmes, Aix Marseille University, APHM, INSERM, Marseille, France.

Jill Richardson (J)

Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.

Ellen De Roeck (E)

Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.

Kristel Sleegers (K)

Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Flanders, Belgium.

Régis Bordet (R)

University of Lille, INSERM, CHU, Degenerative and Vascular Cognitive Disorders, Lille, Lille, France.

Lorena Rami (L)

Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic-IDIBAPS, Barcelona, Spain.

Petronella Kettunen (P)

Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Memory Clinic at Department of Neuropsychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden; Nuffield Department of Clinical Neurosciences, University of Oxford, West Wing, John Radcliffe Hospital, Oxford, UK.

Magda Tsolaki (M)

First Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.

Frans Verhey (F)

Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands.

Isabel Sala (I)

Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Alberto Lléo (A)

Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Gwendoline Peyratout (G)

University Hospital of Lausanne, Lausanne, Switzerland.

Mikel Tainta (M)

CITA-Alzheimer Foundation, San Sebastian, Spain.

Peter Johannsen (P)

Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Yvonne Freund-Levi (Y)

Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.

Lutz Frölich (L)

Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.

Valerija Dobricic (V)

Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Germany.

Sebastiaan Engelborghs (S)

Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Germany; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.

Giovanni B Frisoni (GB)

University of Geneva, Geneva, Switzerland.

José L Molinuevo (JL)

Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic-IDIBAPS, Barcelona, Spain; Barcelona Beta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.

Anders Wallin (A)

Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Julius Popp (J)

University Hospital of Lausanne, Lausanne, Switzerland; Geriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland.

Pablo Martinez-Lage (P)

CITA-Alzheimer Foundation, San Sebastian, Spain.

Lars Bertram (L)

University of Lübeck, Lübeck, Germany.

Frederik Barkhof (F)

Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam University Medical Centers, Amsterdam Neuroscience, Amsterdam, The Netherlands.

Nicholas Ashton (N)

Steno Diabetes Center Copenhagen, Gentofte, Denmark; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Kaj Blennow (K)

Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Henrik Zetterberg (H)

Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.

Johannes Streffer (J)

Experimental Medicine, Janssen Pharmaceutical Companies, Beerse, Belgium.

Pieter J Visser (PJ)

Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands; Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam University Medical Centers, Amsterdam Neuroscience, Amsterdam, The Netherlands.

Simon Lovestone (S)

Department of Psychiatry, University of Oxford, Oxford, UK.

Cristina Legido-Quigley (C)

Institute of Pharmaceutical Science, King's College London, London, UK; Steno Diabetes Center Copenhagen, Gentofte, Denmark. Electronic address: cristina.legido.quigley@regionh.dk.

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Classifications MeSH