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Identification of plasma metabolites associated with modifiable risk factors and endophenotypes reflecting Alzheimer's disease pathology

Dong, R; Denier-Fields, DN; Van Hulle, CA; Kollmorgen, G; Suridjan, I; Wild, N; Lu, Q; ... Engelman, CD; + view all (2023) Identification of plasma metabolites associated with modifiable risk factors and endophenotypes reflecting Alzheimer's disease pathology. European Journal of Epidemiology , 38 pp. 559-571. 10.1007/s10654-023-00988-4. Green open access

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Abstract

Modifiable factors can influence the risk for Alzheimer’s disease (AD) and serve as targets for intervention; however, the biological mechanisms linking these factors to AD are unknown. This study aims to identify plasma metabolites associated with modifiable factors for AD, including MIND diet, physical activity, smoking, and caffeine intake, and test their association with AD endophenotypes to identify their potential roles in pathophysiological mechanisms. The association between each of the 757 plasma metabolites and four modifiable factors was tested in the wisconsin registry for Alzheimer’s prevention cohort of initially cognitively unimpaired, asymptomatic middle-aged adults. After Bonferroni correction, the significant plasma metabolites were tested for association with each of the AD endophenotypes, including twelve cerebrospinal fluid (CSF) biomarkers, reflecting key pathophysiologies for AD, and four cognitive composite scores. Finally, causal mediation analyses were conducted to evaluate possible mediation effects. Analyses were performed using linear mixed-effects regression. A total of 27, 3, 23, and 24 metabolites were associated with MIND diet, physical activity, smoking, and caffeine intake, respectively. Potential mediation effects include beta-cryptoxanthin in the association between MIND diet and preclinical Alzheimer cognitive composite score, hippurate between MIND diet and immediate learning, glutamate between physical activity and CSF neurofilament light, and beta-cryptoxanthin between smoking and immediate learning. Our study identified several plasma metabolites that are associated with modifiable factors. These metabolites can be employed as biomarkers for tracking these factors, and they provide a potential biological pathway of how modifiable factors influence the human body and AD risk.

Type: Article
Title: Identification of plasma metabolites associated with modifiable risk factors and endophenotypes reflecting Alzheimer's disease pathology
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s10654-023-00988-4
Publisher version: https://doi.org/10.1007/s10654-023-00988-4
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 biomarkers, Caffeine, Cognition, MIND diet, Mediation, Physical activity, Plasma metabolites, Smoking
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10168689
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