Journal Article

The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease

Engelman, Corinne D., Carlsson, Cynthia M., Bendlin, Barbara B., Vogt, Nicholas M., Johnson, Sterling C., Blennow, Kaj, Zetterberg, Henrik, Asthana, Sanjay, Rey, Federico E., Romano, Kymberleigh A., Darst, Burcu F.

2018

Overview

Background Trimethylamine N -oxide (TMAO), a small molecule produced by the metaorganismal metabolism of dietary choline, has been implicated in human disease pathogenesis, including known risk factors for Alzheimer’s disease (AD), such as metabolic, cardiovascular, and cerebrovascular disease. Methods In this study, we tested whether TMAO is linked to AD by examining TMAO levels in cerebrospinal fluid (CSF) collected from a large sample ( n  = 410) of individuals with Alzheimer’s clinical syndrome ( n  = 40), individuals with mild cognitive impairment (MCI) ( n  = 35), and cognitively-unimpaired individuals ( n  = 335). Linear regression analyses were used to determine differences in CSF TMAO between groups (controlling for age, sex, and APOE ε4 genotype), as well as to determine relationships between CSF TMAO and CSF biomarkers of AD (phosphorylated tau and beta-amyloid) and neuronal degeneration (total tau, neurogranin, and neurofilament light chain protein). Results CSF TMAO is higher in individuals with MCI and AD dementia compared to cognitively-unimpaired individuals, and elevated CSF TMAO is associated with biomarkers of AD pathology (phosphorylated tau and phosphorylated tau/Aβ 42 ) and neuronal degeneration (total tau and neurofilament light chain protein). Conclusions These findings provide additional insight into gut microbial involvement in AD and add to the growing understanding of the gut–brain axis.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Alzheimer Disease - cerebrospinal fluid / Alzheimer Disease - microbiology / Alzheimer's disease / Amine oxides / Amyloid beta-Peptides - cerebrospinal fluid / Bacteria / Biomarkers / Biomarkers - cerebrospinal fluid / Biomedical and Life Sciences / Biomedicine / Brain research / Cerebrospinal fluid / Cognitive ability / Cognitive Dysfunction - cerebrospinal fluid / Cognitive Dysfunction - microbiology / Dementia / Development and progression / Diabetes / Digestive system / Female / Gastrointestinal Microbiome / Geriatric Psychiatry / Geriatrics/Gerontology / Gut bacteria / Health aspects / Humans / Kinases / Male / Mass spectrometry / Metabolism / Metabolites / Methylamines - cerebrospinal fluid / Microbiota / Microbiota (Symbiotic organisms) / Middle Aged / Mild cognitive impairment / Nervous system / Neurology / Neurosciences / Neurovetenskaper / Oxidative stress / Pathology / Peptide Fragments - cerebrospinal fluid / Physiological aspects / Proteins / Scientific imaging / Stroke / tau Proteins - cerebrospinal fluid / Thrombosis / Trimethylamine N-oxide