Browsing by Author "Bhattacharyya, Sudeepa"

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    Altered bile acid profile associates with cognitive impairment in Alzheimer's disease—An emerging role for gut microbiome
    (Elsevier, 2019-01) MahmoudianDehkordi, Siamak; Arnold, Matthias; Nho, Kwangsik; Ahmad, Shahzad; Jia, Wei; Xie, Guoxiang; Louie, Gregory; Kueider‐Paisley, Alexandra; Moseley, M. Arthur; Thompson, J. Will; St John Williams, Lisa; Tenenbaum, Jessica D.; Blach, Colette; Baillie, Rebecca; Han, Xianlin; Bhattacharyya, Sudeepa; Toledo, Jon B.; Schafferer, Simon; Klein, Sebastian; Koal, Therese; Risacher, Shannon L.; Kling, Mitchel Allan; Motsinger‐Reif, Alison; Rotroff, Daniel M.; Jack, John; Hankemeier, Thomas; Bennett, David A.; De Jager, Philip L.; Trojanowski, John Q.; Shaw, Leslie M.; Weiner, Michael W.; Doraiswamy, P. Murali; van Duijn, Cornelia M.; Saykin, Andrew J.; Kastenmüller, Gabi; Kaddurah‐Daouk, Rima; Radiology and Imaging Sciences, School of Medicine
    Introduction Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut‐brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer's disease (AD). Methods Serum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 AD cases enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD‐related genetic variants, adjusting for confounders and multiple testing. Results In AD compared to cognitively normal older adults, we observed significantly lower serum concentrations of a primary BA (cholic acid [CA]) and increased levels of the bacterially produced, secondary BA, deoxycholic acid, and its glycine and taurine conjugated forms. An increased ratio of deoxycholic acid:CA, which reflects 7α‐dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response–related genes implicated in AD showed associations with BA profiles. Discussion We report for the first time an association between altered BA profile, genetic variants implicated in AD, and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut‐liver‐brain axis in the pathogenesis of AD.
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    Serum triglycerides in Alzheimer disease: Relation to neuroimaging and CSF biomarkers
    (Wolters Kluwer, 2020-05-01) Bernath, Megan M.; Bhattacharyya, Sudeepa; Nho, Kwangsik; Barupal, Dinesh Kumar; Fiehn, Oliver; Baillie, Rebecca; Risacher, Shannon L.; Arnold, Matthias; Jacobson, Tanner; Trojanowski, John Q.; Shaw, Leslie M.; Weiner, Michael W.; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Saykin, Andrew J.; Consortium for the Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Metabolomics; Medicine, School of Medicine
    Objective To investigate the association of triglyceride (TG) principal component scores with Alzheimer disease (AD) and the amyloid, tau, neurodegeneration, and cerebrovascular disease (A/T/N/V) biomarkers for AD. Methods Serum levels of 84 TG species were measured with untargeted lipid profiling of 689 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, including 190 cognitively normal older adults (CN), 339 with mild cognitive impairment (MCI), and 160 with AD. Principal component analysis with factor rotation was used for dimension reduction of TG species. Differences in principal components between diagnostic groups and associations between principal components and AD biomarkers (including CSF, MRI and [18F]fluorodeoxyglucose-PET) were assessed with a generalized linear model approach. In both cases, the Bonferroni method of adjustment was used to correct for multiple comparisons. Results The 84 TGs yielded 9 principal components, 2 of which, consisting of long-chain, polyunsaturated fatty acid–containing TGs (PUTGs), were significantly associated with MCI and AD. Lower levels of PUTGs were observed in MCI and AD compared to CN. PUTG principal component scores were also significantly associated with hippocampal volume and entorhinal cortical thickness. In participants carrying the APOE ε4 allele, these principal components were significantly associated with CSF β-amyloid1–42 values and entorhinal cortical thickness. Conclusion This study shows that PUTG component scores were significantly associated with diagnostic group and AD biomarkers, a finding that was more pronounced in APOE ε4 carriers. Replication in independent larger studies and longitudinal follow-up are warranted.