Dong, Ruocheng;
Denier-Fields, Diandra N;
Lu, Qiongshi;
Suridjan, Ivonne;
Kollmorgen, Gwendlyn;
Wild, Norbert;
Betthauser, Tobey James;
... Engelman, Corinne D; + view all
(2022)
Principal components from untargeted cerebrospinal fluid metabolomics associated with Alzheimer's disease biomarkers.
Neurobiology of Aging
, 117
pp. 12-23.
10.1016/j.neurobiolaging.2022.04.009.
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Abstract
Studying the correlation between cerebrospinal fluid (CSF) metabolites and the Alzheimer's Disease (AD) biomarkers may offer a window to the alterations of the brain metabolome and unveil potential biological mechanisms underlying AD. In this analysis, 308 CSF metabolites from 338 individuals of Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center were included in a principal component analysis (PCA). The resulted principal components (PCs) were tested for association with CSF total tau (t-tau), phosphorylated tau (p-tau), amyloid β 42 (Aβ42), and Aβ42/40 ratio using linear regression models. Significant PCs were further tested with other CSF NeuroToolKit (NTK) and imaging biomarkers. Using a Bonferroni corrected p < 0.05, 5 PCs were significantly associated with CSF p-tau and t-tau and 3 PCs were significantly associated with CSF Aβ42. Pathway analysis suggested that these PCS were enriched in 6 pathways, including metabolism of caffeine and nicotinate and nicotinamide. This study provides evidence that CSF metabolites are associated with AD pathology through core AD biomarkers and other NTK markers and suggests potential pathways to follow up in future studies.
| Type: | Article |
|---|---|
| Title: | Principal components from untargeted cerebrospinal fluid metabolomics associated with Alzheimer's disease biomarkers |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neurobiolaging.2022.04.009 |
| Publisher version: | https://doi.org/10.1016/j.neurobiolaging.2022.04.0... |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Alzheimer's disease, Amyloid β 42/40, CSF metabolomics, Phosphorylated tau, Principal component analysis, Total tau |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10150815 |
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