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

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.

A metabolite‐based machine learning approach to diagnose Alzheimer‐type dementia in blood: Results from the European Medical Information Framework for Alzheimer disease biomarker discovery cohort

“…In this study, we analyzed metabolite data derived from blood samples from 357 participants (CN n = 242, AD n = 115) previously reported in Kim et al. [7]. Demographic and clinical data can be found in [7]; in short, there was no difference in gender while AD participants were older when compared with CN participants.…”

“…[7]. Demographic and clinical data can be found in [7]; in short, there was no difference in gender while AD participants were older when compared with CN participants.…”

“…This study accessed data previously generated from 242 samples from cognitively normal (CN) individuals and 115 from people with AD‐type dementia (AD) samples in which diagnosis was based on clinical diagnosis. Details on the subjects, clinical and cognitive data, as well as measurements of AD pathological markers have been described elsewhere [7,8]. The metabolomics data employed here was accessed in the EMIF‐AD portal and the acquisition and processing details can be found via open access in [7].…”

“…Details on the subjects, clinical and cognitive data, as well as measurements of AD pathological markers have been described elsewhere [7,8]. The metabolomics data employed here was accessed in the EMIF‐AD portal and the acquisition and processing details can be found via open access in [7]. In short, the EMIF‐AD cohort is a collated cohort making use of existing data and samples collected in 11 different studies across Europe, with the aim to discover novel diagnostic and prognostic markers for predementia AD.…”

“…Here we utilized data generated as part of the European Medical Information Framework for AD Multimodal Biomarker Discovery (EMIF‐AD) previously reported in full in Kim et al. [7]. As discussed in that paper, metabolite levels were measured using liquid chromatography–mass spectroscopy (LC‐MS) to cover ca.…”