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
Min Kim
(1)
,
Stuart Snowden
(2)
,
Tommi Suvitaival
(3)
,
Ashfaq Ali
(3)
,
David Merkler
(4)
,
Tahmina Ahmad
(1)
,
Sarah Westwood
(5)
,
Alison Baird
(5)
,
Petroula Proitsi
(1)
,
Alejo Nevado‐holgado
(5)
,
Abdul Hye
(3)
,
Isabelle Bos
(6)
,
Stephanie Vos
(6)
,
Rik Vandenberghe
(7)
,
Charlotte Teunissen
(8)
,
Mara Kate
(8)
,
Philip Scheltens
(8)
,
Silvy Gabel
(9)
,
Karen Meersmans
(9)
,
Olivier Blin
(10, 11)
,
Jill Richardson
(12)
,
Ellen de Roeck
(13)
,
Kristel Sleegers
(13)
,
Régis Bordet
(14, 15)
,
Lorena Rami
(16)
,
Petronella Kettunen
(17, 5)
,
Magda Tsolaki
(18)
,
Frans Verhey
(6)
,
Isabel Sala
(19)
,
Alberto Lléo
(19)
,
Gwendoline Peyratout
(20)
,
Mikel Tainta
(21)
,
Peter Johannsen
(22)
,
Yvonne Freund‐levi
(23)
,
Lutz Frölich
(24)
,
Valerija Dobricic
(25)
,
Sebastiaan Engelborghs
(13, 25)
,
Giovanni Frisoni
(26)
,
José Molinuevo
(16)
,
Anders Wallin
(17)
,
Julius Popp
(27, 20)
,
Pablo Martinez‐lage
(21)
,
Lars Bertram
(25)
,
Frederik Barkhof
(8)
,
Nicholas Ashton
(17)
,
Kaj Blennow
(17, 28)
,
Henrik Zetterberg
(17, 28, 29)
,
Johannes Streffer
(30)
,
Pieter Visser
(6, 8)
,
Simon Lovestone
(5)
,
Cristina Legido‐quigley
(1, 3)
1
King‘s College London
2 CAM - University of Cambridge [UK]
3 Steno Diabetes Center of Copenhagen [Gentofte, Denmark]
4 USF - University of South Florida [Tampa]
5 University of Oxford
6 Maastricht University [Maastricht]
7 University Hospitals Leuven [Leuven]
8 Amsterdam UMC - Amsterdam University Medical Center
9 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
10 INS - Institut de Neurosciences des Systèmes
11 APHM - Assistance Publique - Hôpitaux de Marseille
12 GSK - GlaxoSmithKline [Stevenage, UK]
13 UA - University of Antwerp
14 Troubles cognitifs vasculaires et dégénératifs
15 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
16 IDIBAPS - Hospital Clinic
17 GU - Göteborgs Universitet = University of Gothenburg
18 AHEPA University General Hospital [Thessaloniki]
19 Hospital de la Santa Creu i Sant Pau
20 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
21 Center for Research and Advanced Therapies CITA-Alzheimer Foundation [San Sebastián]
22 Copenhagen University Hospital
23 Karolinska University Hospital [Stockholm]
24 Universität Heidelberg [Heidelberg] = Heidelberg University
25 Universität zu Lübeck = University of Lübeck [Lübeck]
26 UNIGE - Université de Genève = University of Geneva
27 HUG - Geneva University Hospital
28 Sahlgrenska University Hospital [Gothenburg]
29 UCL Queen Square Institute of Neurology
30 Janssen Pharmaceutica [Beerse]
2 CAM - University of Cambridge [UK]
3 Steno Diabetes Center of Copenhagen [Gentofte, Denmark]
4 USF - University of South Florida [Tampa]
5 University of Oxford
6 Maastricht University [Maastricht]
7 University Hospitals Leuven [Leuven]
8 Amsterdam UMC - Amsterdam University Medical Center
9 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
10 INS - Institut de Neurosciences des Systèmes
11 APHM - Assistance Publique - Hôpitaux de Marseille
12 GSK - GlaxoSmithKline [Stevenage, UK]
13 UA - University of Antwerp
14 Troubles cognitifs vasculaires et dégénératifs
15 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
16 IDIBAPS - Hospital Clinic
17 GU - Göteborgs Universitet = University of Gothenburg
18 AHEPA University General Hospital [Thessaloniki]
19 Hospital de la Santa Creu i Sant Pau
20 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
21 Center for Research and Advanced Therapies CITA-Alzheimer Foundation [San Sebastián]
22 Copenhagen University Hospital
23 Karolinska University Hospital [Stockholm]
24 Universität Heidelberg [Heidelberg] = Heidelberg University
25 Universität zu Lübeck = University of Lübeck [Lübeck]
26 UNIGE - Université de Genève = University of Geneva
27 HUG - Geneva University Hospital
28 Sahlgrenska University Hospital [Gothenburg]
29 UCL Queen Square Institute of Neurology
30 Janssen Pharmaceutica [Beerse]
Olivier Blin
- Fonction : Auteur
- PersonId : 780347
- ORCID : 0000-0003-0142-0931
Giovanni Frisoni
- Fonction : Auteur
- PersonId : 768850
- ORCID : 0000-0001-7075-7082
Frederik Barkhof
- Fonction : Auteur
- PersonId : 772998
- ORCID : 0000-0003-3543-3706
- IdRef : 138520682
Nicholas Ashton
- Fonction : Auteur
- PersonId : 821859
- ORCID : 0000-0002-3579-8804
Kaj Blennow
- Fonction : Auteur
- PersonId : 763020
- ORCID : 0000-0002-1890-4193
Henrik Zetterberg
- Fonction : Auteur
- PersonId : 763019
- ORCID : 0000-0003-3930-4354
Résumé
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.