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Alzheimers Dement. 2019 Jun;15(6):817-827. doi: 10.1016/j.jalz.2019.03.004. Epub 2019 May 8.

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.

Author information

1
Institute of Pharmaceutical Science, King's College London, London, UK; Steno Diabetes Center Copenhagen, Gentofte, Denmark.
2
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.
3
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
4
Department of Chemistry, University of South Florida, Tampa, FL, USA.
5
Institute of Pharmaceutical Science, King's College London, London, UK.
6
Department of Psychiatry, University of Oxford, Oxford, UK.
7
Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
8
Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands.
9
University Hospital Leuven, Leuven, Belgium.
10
Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam University Medical Centers, Amsterdam Neuroscience, Amsterdam, The Netherlands.
11
Department of Neurology, Alzheimer Center, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
12
University Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
13
Service de Pharmacologie Clinique et Pharmacovigilance, Institut de Neurosciences des Systèmes, Aix Marseille University, APHM, INSERM, Marseille, France.
14
Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.
15
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
16
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Flanders, Belgium.
17
University of Lille, INSERM, CHU, Degenerative and Vascular Cognitive Disorders, Lille, Lille, France.
18
Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic-IDIBAPS, Barcelona, Spain.
19
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.
20
First Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.
21
Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
22
University Hospital of Lausanne, Lausanne, Switzerland.
23
CITA-Alzheimer Foundation, San Sebastian, Spain.
24
Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
25
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.
26
Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
27
Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Germany.
28
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.
29
University of Geneva, Geneva, Switzerland.
30
Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic-IDIBAPS, Barcelona, Spain; Barcelona Beta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
31
Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
32
University Hospital of Lausanne, Lausanne, Switzerland; Geriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland.
33
University of Lübeck, Lübeck, Germany.
34
Steno Diabetes Center Copenhagen, Gentofte, Denmark; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
35
Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
36
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.
37
Experimental Medicine, Janssen Pharmaceutical Companies, Beerse, Belgium.
38
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.
39
Institute of Pharmaceutical Science, King's College London, London, UK; Steno Diabetes Center Copenhagen, Gentofte, Denmark. Electronic address: cristina.legido.quigley@regionh.dk.

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.

KEYWORDS:

Alzheimer's disease; Amyloid; Biomarkers; Brain volume measurements; CSF; Cognitive function measurements; Dementia; EMIF-AD; Metabolomics; Tau

PMID:
31078433
DOI:
10.1016/j.jalz.2019.03.004
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