Serum Bile Acids Improve Prediction of Alzheimer's Progression in a Sex-Dependent Manner

Tianlu Chen, Lu Wang, Guoxiang Xie, Bruce S. Kristal, Xiaojiao Zheng, Tao Sun, Matthias Arnold, Gregory Louie, Mengci Li, Lirong Wu, Siamak Mahmoudiandehkordi, Matthew J. Sniatynski, Kamil Borkowski, Qihao Guo, Junliang Kuang, Jieyi Wang, Kwangsik Nho, Zhenxing Ren, Alexandra Kueider-Paisley, Colette BlachRima Kaddurah-Daouk*, Wei Jia*, Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Alzheimer Disease Metabolomics Consortium (ADMC)

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

1 Citation (Scopus)


Sex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes in serum BAs and AD development remains elusive. Here, authors quantitatively determined 33 serum BAs and 58 BA features in 4 219 samples collected from 1 180 participants from the Alzheimer's Disease Neuroimaging Initiative. The findings revealed that these BA features exhibited significant correlations with clinical stages, encompassing cognitively normal (CN), early and late mild cognitive impairment, and AD, as well as cognitive performance. Importantly, these associations are more pronounced in men than women. Among participants with progressive disease stages (n = 660), BAs underwent early changes in men, occurring before AD. By incorporating BA features into diagnostic and predictive models, positive enhancements are achieved for all models. The area under the receiver operating characteristic curve improved from 0.78 to 0.91 for men and from 0.76 to 0.83 for women for the differentiation of CN and AD. Additionally, the key findings are validated in a subset of participants (n = 578) with cerebrospinal fluid amyloid-beta and tau levels. These findings underscore the role of BAs in AD progression, offering potential improvements in the accuracy of AD prediction.

Original languageEnglish
Article number2306576
Number of pages13
JournalAdvanced Science
Issue number9
Early online date13 Dec 2023
Publication statusPublished - 6 Mar 2024

Scopus Subject Areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

User-Defined Keywords

  • alzheimer's disease
  • bile acid
  • cholesterol
  • mild cognitive impairment
  • sex difference


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