TY - JOUR
T1 - Serum Bile Acids Improve Prediction of Alzheimer's Progression in a Sex-Dependent Manner
AU - Chen, Tianlu
AU - Wang, Lu
AU - Xie, Guoxiang
AU - Kristal, Bruce S.
AU - Zheng, Xiaojiao
AU - Sun, Tao
AU - Arnold, Matthias
AU - Louie, Gregory
AU - Li, Mengci
AU - Wu, Lirong
AU - Mahmoudiandehkordi, Siamak
AU - Sniatynski, Matthew J.
AU - Borkowski, Kamil
AU - Guo, Qihao
AU - Kuang, Junliang
AU - Wang, Jieyi
AU - Nho, Kwangsik
AU - Ren, Zhenxing
AU - Kueider-Paisley, Alexandra
AU - Blach, Colette
AU - Kaddurah-Daouk, Rima
AU - Jia, Wei
AU - Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Alzheimer Disease Metabolomics Consortium (ADMC)
N1 - Funding information:
This work was supported by National Institutes of Health (NIH; NIA: R01AG046171, RF1AG051550, RF1AG057452, R01AG059093, RF1AG058942, U01AG061359, and U19AG063744; FNIH: #DAOU16AMPA awarded to Dr. Kaddurah-Daouk at Duke University in partnership with a large number of academic institutions). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. The metabolomics data were provided by the Alzheimer's Disease Metabolomics Consortium (ADMC). As such, the investigators within the ADMC, not listed specifically in this publication's author's list, provided data along with its pre-processing and prepared it for analysis, but did not participate in analysis or writing of this manuscript. The authors are grateful to Lisa Howerton for administrative support.
Publisher Copyright:
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH
PY - 2024/3/6
Y1 - 2024/3/6
N2 - 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.
AB - 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.
KW - alzheimer's disease
KW - bile acid
KW - cholesterol
KW - mild cognitive impairment
KW - sex difference
UR - http://www.scopus.com/inward/record.url?scp=85179918977&partnerID=8YFLogxK
U2 - 10.1002/advs.202306576
DO - 10.1002/advs.202306576
M3 - Journal article
AN - SCOPUS:85179918977
SN - 2198-3844
VL - 11
JO - Advanced Science
JF - Advanced Science
IS - 9
M1 - 2306576
ER -
