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Alzheimers Res Ther. 2018 Dec 22;10(1):124. doi: 10.1186/s13195-018-0451-2.

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

Author information

1
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
2
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
3
Present Address: Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH, USA.
4
Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
5
Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
6
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
7
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
8
Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, UK.
9
UK Dementia Research Institute at University College London, London, UK.
10
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. bbb@medicine.wisc.edu.
11
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA. ferey@wisc.edu.

Abstract

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/Aβ42) 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.

KEYWORDS:

Alzheimer’s disease; Amyloid; Biomarkers; Cerebrospinal fluid; Gut bacteria; Microbiota; Neurofilament light; Tau; Trimethylamine N-oxide

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