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

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


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.

Publication types

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

MeSH terms

  • Aged
  • Amyloid beta-Peptides* / blood
  • Amyloid beta-Peptides* / cerebrospinal fluid
  • Amyloidosis / blood*
  • Amyloidosis / cerebrospinal fluid
  • Amyloidosis / metabolism
  • Biomarkers* / blood
  • Biomarkers* / cerebrospinal fluid
  • Brain / pathology
  • Cognitive Dysfunction / diagnosis
  • Cohort Studies
  • Female
  • Hippocampus* / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory / physiology*
  • Metabolomics*
  • Middle Aged
  • Neuropsychological Tests
  • tau Proteins / blood
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins