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

Autor: Kaj Blennow, Sterling C. Johnson, Federico E. Rey, Nicholas M. Vogt, Sanjay Asthana, Henrik Zetterberg, Corinne D. Engelman, Burcu F. Darst, Cynthia M. Carlsson, Kymberleigh A. Romano, Barbara B. Bendlin
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Trimethylamine N-oxide
Gut flora
lcsh:RC346-429
Pathogenesis
chemistry.chemical_compound
0302 clinical medicine
Cerebrospinal fluid
Choline
Neurogranin
Gut bacteria
biology
Microbiota
Middle Aged
3. Good health
Neurology
Female
Alzheimer's disease
Alzheimer’s disease
medicine.medical_specialty
Amyloid
Neurofilament light
Cognitive Neuroscience
tau Proteins
lcsh:RC321-571
03 medical and health sciences
Methylamines
Alzheimer Disease
Internal medicine
medicine
Dementia
Humans
Cognitive Dysfunction
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
lcsh:Neurology. Diseases of the nervous system
Aged
Amyloid beta-Peptides
business.industry
Research
medicine.disease
biology.organism_classification
Peptide Fragments
Gastrointestinal Microbiome
030104 developmental biology
Endocrinology
chemistry
Neurology (clinical)
Tau
business
030217 neurology & neurosurgery
Biomarkers
Zdroj: Alzheimer's Research & Therapy
Alzheimers Research & Therapy
Alzheimer’s Research & Therapy, Vol 10, Iss 1, Pp 1-8 (2018)
ISSN: 1758-9193
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s13195-018-0451-2) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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