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

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.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).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).These findings provide additional insight into gut microbial involvement in AD and add to the growing understanding of the gut-brain axis.

Romano, Kymberleigh A (author)
Darst, Burcu F (author)
Engelman, Corinne D (author)
Johnson, Sterling C (author)
Carlsson, Cynthia M (author)
Asthana, Sanjay (author)
Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka (author)
Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe (author)
Bendlin, Barbara B (author)
Rey, Federico E (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

In:Alzheimer's research & therapy: Springer Science and Business Media LLC10:11758-9193

By the author/editor: Vogt, Nicholas M; Romano, Kymberle ...; Darst, Burcu F; Engelman, Corinn ...; Johnson, Sterlin ...; Carlsson, Cynthi ...; show more...; Asthana, Sanjay; Blennow, Kaj, 19 ...; Zetterberg, Henr ...; Bendlin, Barbara ...; Rey, Federico E; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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