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, Stuart Snowden, Tommi Suvitaival, Ashfaq Ali, David J. Merkler, Tahmina Ahmad, Sarah Westwood, Alison Baird, Petroula Proitsi, Alejo Nevado-Holgado, Abdul Hye, Isabelle Bos, Stephanie Vos, Rik Vandenberghe, Charlotte Teunissen, Mara ten Kate, Philip Scheltens, Silvy Gabel, Karen Meersmans, Olivier BlinJill Richardson, Ellen De Roeck, Kristel Sleegers, Regis Bordet, Lorena Rami, Petronella Kettunen, Magda Tsolaki, Frans Verhey, Isabel Sala, Alberto Lleo, Gwendoline Peyratout, Mikel Tainta, Peter Johannsen, Yvonne Freund-Levi, Lutz Frolich, Valerija Dobricic, Sebastiaan Engelborghs, Giovanni B. Frisoni, Jose L. Molinuevo, Anders Wallin, Julius Popp, Pablo Martinez-Lage, Lars Bertram, Frederik Barkhof, Nicholas Ashton, Kaj Blennow, Henrik Zetterberg, Johannes Streffer, Pieter J. Visser, Simon Lovestone, Cristina Legido-Quigley*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 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/).

Original languageEnglish
Pages (from-to)817-827
Number of pages11
JournalAlzheimer's & Dementia
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 2019

Keywords

  • EMIF-AD
  • Alzheimer's disease
  • Dementia
  • Amyloid
  • Tau
  • CSF
  • Brain volume measurements
  • Cognitive function measurements
  • Metabolomics
  • Biomarkers
  • INDUCED LIPOKINE
  • ACID
  • OLEAMIDE
  • MARKERS
  • RECOMMENDATIONS
  • PERTURBATIONS
  • BIOSYNTHESIS
  • METABOLOMICS
  • 12,13-DIHOME
  • METABOLISM

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