Browsing by Author "Kristal, Bruce S."

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    Circulating lipid profiles are associated with cross-sectional and longitudinal changes of central biomarkers for Alzheimer's disease
    (medRxiv, 2023-06-21) Kim, Jun Pyo; Nho, Kwangsik; Wang, Tingting; Huynh, Kevin; Arnold, Matthias; Risacher, Shannon L.; Bice, Paula J.; Han, Xianlin; Kristal, Bruce S.; Blach, Colette; Baillie, Rebecca; Kastenmüller, Gabi; Meikle, Peter J.; Saykin, Andrew J.; Kaddurah-Daouk, Rima; Alzheimer’s Disease Neuroimaging Initiative; Alzheimer’s Disease Metabolomics Consortium; Radiology and Imaging Sciences, School of Medicine
    Investigating the association of lipidome profiles with central Alzheimer's disease (AD) biomarkers, including amyloid/tau/neurodegeneration (A/T/N), can provide a holistic view between the lipidome and AD. We performed cross-sectional and longitudinal association analysis of serum lipidome profiles with AD biomarkers in the Alzheimer's Disease Neuroimaging Initiative cohort (N=1,395). We identified lipid species, classes, and network modules that were significantly associated with cross-sectional and longitudinal changes of A/T/N biomarkers for AD. Notably, we identified the lysoalkylphosphatidylcholine (LPC(O)) as associated with "A/N" biomarkers at baseline at lipid species, class, and module levels. Also, GM3 ganglioside showed significant association with baseline levels and longitudinal changes of the "N" biomarkers at species and class levels. Our study of circulating lipids and central AD biomarkers enabled identification of lipids that play potential roles in the cascade of AD pathogenesis. Our results suggest dysregulation of lipid metabolic pathways as precursors to AD development and progression.
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    Serum Bile Acids Improve Prediction of Alzheimer's Progression in a Sex-Dependent Manner
    (Wiley, 2024) Chen, Tianlu; Wang, Lu; Xie, Guoxiang; Kristal, Bruce S.; Zheng, Xiaojiao; Sun, Tao; Arnold, Matthias; Louie, Gregory; Li, Mengci; Wu, Lirong; Mahmoudiandehkordi, Siamak; Sniatynski, Matthew J.; Borkowski, Kamil; Guo, Qihao; Kuang, Junliang; Wang, Jieyi; Nho, Kwangsik; Ren, Zhenxing; Kueider-Paisley, Alexandra; Blach, Colette; Kaddurah-Daouk, Rima; Jia, Wei; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Alzheimer Disease Metabolomics Consortium (ADMC); Radiology and Imaging Sciences, School of Medicine
    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.