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 |
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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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