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Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer’s Disease

Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile acid synthesis pathway to be expressed...

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Published in:Cell reports. Medicine 2020-11, Vol.1 (8), p.100138, Article 100138
Main Authors: Baloni, Priyanka, Funk, Cory C., Yan, Jingwen, Yurkovich, James T., Kueider-Paisley, Alexandra, Nho, Kwangsik, Heinken, Almut, Jia, Wei, Mahmoudiandehkordi, Siamak, Louie, Gregory, Saykin, Andrew J., Arnold, Matthias, Kastenmüller, Gabi, Griffiths, William J., Thiele, Ines, Kaddurah-Daouk, Rima, Doraiswamy, P. Murali, Blach, Colette, Moseley, Arthur, Thompson, J. Will, Mahmoudiandehkhordi, Siamak, Welsh-Balmer, Kathleen, Plassman, Brenda, Saykin, Andrew, Bhattacharyya, Sudeepa, Han, Xianlin, Baillie, Rebecca, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Kling, Mitchel, Shaw, Leslie, Trojanowski, John, Toledo, Jon, van Duijin, Cornelia, Hankemier, Thomas, Price, Nathan, Funk, Cory, Wishart, David, Brinton, Roberta, Chang, Rui, Farrer, Lindsay, Au, Rhoda, Qiu, Wendy, Würtz, Peter, Mangravite, Lara, Krumsiek, Jan, Newman, John, Zhang, Bin, Moreno, Herman, Price, Nathan D.
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creator Baloni, Priyanka
Funk, Cory C.
Yan, Jingwen
Yurkovich, James T.
Kueider-Paisley, Alexandra
Nho, Kwangsik
Heinken, Almut
Jia, Wei
Mahmoudiandehkordi, Siamak
Louie, Gregory
Saykin, Andrew J.
Arnold, Matthias
Kastenmüller, Gabi
Griffiths, William J.
Thiele, Ines
Kaddurah-Daouk, Rima
Kueider-Paisley, Alexandra
Louie, Gregory
Doraiswamy, P. Murali
Blach, Colette
Moseley, Arthur
Thompson, J. Will
Mahmoudiandehkhordi, Siamak
Welsh-Balmer, Kathleen
Plassman, Brenda
Saykin, Andrew
Nho, Kwangsik
Kastenmüller, Gabi
Arnold, Matthias
Bhattacharyya, Sudeepa
Han, Xianlin
Baillie, Rebecca
Fiehn, Oliver
Barupal, Dinesh
Meikle, Peter
Mazmanian, Sarkis
Kling, Mitchel
Shaw, Leslie
Trojanowski, John
Toledo, Jon
van Duijin, Cornelia
Hankemier, Thomas
Thiele, Ines
Heinken, Almut
Price, Nathan
Funk, Cory
Baloni, Priyanka
Jia, Wei
Wishart, David
Brinton, Roberta
Chang, Rui
Farrer, Lindsay
Au, Rhoda
Qiu, Wendy
Würtz, Peter
Mangravite, Lara
Krumsiek, Jan
Newman, John
Zhang, Bin
Moreno, Herman
Kaddurah-Daouk, Rima
Price, Nathan D.
description Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile acid synthesis pathway to be expressed in the brain. A targeted metabolomic analysis of primary and secondary bile acids measured from post-mortem brain samples of 111 individuals supports these results. Our metabolic network analysis suggests that taurine transport, bile acid synthesis, and cholesterol metabolism differ in AD and cognitively normal individuals. We also identify putative transcription factors regulating metabolic genes and influencing altered metabolism in AD. Intriguingly, some bile acids measured in brain tissue cannot be explained by the presence of enzymes responsible for their synthesis, suggesting that they may originate from the gut microbiome and are transported to the brain. These findings motivate further research into bile acid metabolism in AD to elucidate their possible connection to cognitive decline. [Display omitted] Altered cholesterol and bile acid metabolism linked to Alzheimer disease (AD)Evidence for alternative bile acid pathway genes expression in post-mortem brainsMetabolomics analysis shows secondary bile acids associated with cognitive declineGenome-scale metabolic networks of brain regions identify reactions linked to AD Baloni et al. use a systems biology approach to identify alterations in cholesterol and bile acid metabolism in Alzheimer disease (AD). Expression of alternative bile acid and neural cholesterol clearance pathway along with transporters of taurine and bile acids suggest the role of the gut-brain axis in AD.
doi_str_mv 10.1016/j.xcrm.2020.100138
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Murali ; Blach, Colette ; Moseley, Arthur ; Thompson, J. Will ; Mahmoudiandehkhordi, Siamak ; Welsh-Balmer, Kathleen ; Plassman, Brenda ; Saykin, Andrew ; Nho, Kwangsik ; Kastenmüller, Gabi ; Arnold, Matthias ; Bhattacharyya, Sudeepa ; Han, Xianlin ; Baillie, Rebecca ; Fiehn, Oliver ; Barupal, Dinesh ; Meikle, Peter ; Mazmanian, Sarkis ; Kling, Mitchel ; Shaw, Leslie ; Trojanowski, John ; Toledo, Jon ; van Duijin, Cornelia ; Hankemier, Thomas ; Thiele, Ines ; Heinken, Almut ; Price, Nathan ; Funk, Cory ; Baloni, Priyanka ; Jia, Wei ; Wishart, David ; Brinton, Roberta ; Chang, Rui ; Farrer, Lindsay ; Au, Rhoda ; Qiu, Wendy ; Würtz, Peter ; Mangravite, Lara ; Krumsiek, Jan ; Newman, John ; Zhang, Bin ; Moreno, Herman ; Kaddurah-Daouk, Rima ; Price, Nathan D.</creator><creatorcontrib>Baloni, Priyanka ; Funk, Cory C. ; Yan, Jingwen ; Yurkovich, James T. ; Kueider-Paisley, Alexandra ; Nho, Kwangsik ; Heinken, Almut ; Jia, Wei ; Mahmoudiandehkordi, Siamak ; Louie, Gregory ; Saykin, Andrew J. ; Arnold, Matthias ; Kastenmüller, Gabi ; Griffiths, William J. ; Thiele, Ines ; Kaddurah-Daouk, Rima ; Kueider-Paisley, Alexandra ; Louie, Gregory ; Doraiswamy, P. Murali ; Blach, Colette ; Moseley, Arthur ; Thompson, J. Will ; Mahmoudiandehkhordi, Siamak ; Welsh-Balmer, Kathleen ; Plassman, Brenda ; Saykin, Andrew ; Nho, Kwangsik ; Kastenmüller, Gabi ; Arnold, Matthias ; Bhattacharyya, Sudeepa ; Han, Xianlin ; Baillie, Rebecca ; Fiehn, Oliver ; Barupal, Dinesh ; Meikle, Peter ; Mazmanian, Sarkis ; Kling, Mitchel ; Shaw, Leslie ; Trojanowski, John ; Toledo, Jon ; van Duijin, Cornelia ; Hankemier, Thomas ; Thiele, Ines ; Heinken, Almut ; Price, Nathan ; Funk, Cory ; Baloni, Priyanka ; Jia, Wei ; Wishart, David ; Brinton, Roberta ; Chang, Rui ; Farrer, Lindsay ; Au, Rhoda ; Qiu, Wendy ; Würtz, Peter ; Mangravite, Lara ; Krumsiek, Jan ; Newman, John ; Zhang, Bin ; Moreno, Herman ; Kaddurah-Daouk, Rima ; Price, Nathan D. ; The Alzheimer’s Disease Metabolomics Consortium ; Alzheimer’s Disease Metabolomics Consortium</creatorcontrib><description>Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile acid synthesis pathway to be expressed in the brain. A targeted metabolomic analysis of primary and secondary bile acids measured from post-mortem brain samples of 111 individuals supports these results. Our metabolic network analysis suggests that taurine transport, bile acid synthesis, and cholesterol metabolism differ in AD and cognitively normal individuals. We also identify putative transcription factors regulating metabolic genes and influencing altered metabolism in AD. Intriguingly, some bile acids measured in brain tissue cannot be explained by the presence of enzymes responsible for their synthesis, suggesting that they may originate from the gut microbiome and are transported to the brain. These findings motivate further research into bile acid metabolism in AD to elucidate their possible connection to cognitive decline. [Display omitted] Altered cholesterol and bile acid metabolism linked to Alzheimer disease (AD)Evidence for alternative bile acid pathway genes expression in post-mortem brainsMetabolomics analysis shows secondary bile acids associated with cognitive declineGenome-scale metabolic networks of brain regions identify reactions linked to AD Baloni et al. use a systems biology approach to identify alterations in cholesterol and bile acid metabolism in Alzheimer disease (AD). Expression of alternative bile acid and neural cholesterol clearance pathway along with transporters of taurine and bile acids suggest the role of the gut-brain axis in AD.</description><identifier>ISSN: 2666-3791</identifier><identifier>EISSN: 2666-3791</identifier><identifier>DOI: 10.1016/j.xcrm.2020.100138</identifier><identifier>PMID: 33294859</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alzheimer Disease - metabolism ; Alzheimer's disease ; bile acids ; Bile Acids and Salts - metabolism ; Brain - metabolism ; Cholesterol - metabolism ; Cognitive Dysfunction - metabolism ; genome-scale metabolic models ; Humans ; Lipid Metabolism - physiology ; Lipogenesis - physiology ; Metabolic Networks and Pathways - physiology ; metabolomics ; Metabolomics - methods ; transcriptional regulatory networks ; Transcriptome - physiology ; transcriptomics</subject><ispartof>Cell reports. 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Medicine</title><addtitle>Cell Rep Med</addtitle><description>Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile acid synthesis pathway to be expressed in the brain. A targeted metabolomic analysis of primary and secondary bile acids measured from post-mortem brain samples of 111 individuals supports these results. Our metabolic network analysis suggests that taurine transport, bile acid synthesis, and cholesterol metabolism differ in AD and cognitively normal individuals. We also identify putative transcription factors regulating metabolic genes and influencing altered metabolism in AD. Intriguingly, some bile acids measured in brain tissue cannot be explained by the presence of enzymes responsible for their synthesis, suggesting that they may originate from the gut microbiome and are transported to the brain. These findings motivate further research into bile acid metabolism in AD to elucidate their possible connection to cognitive decline. [Display omitted] Altered cholesterol and bile acid metabolism linked to Alzheimer disease (AD)Evidence for alternative bile acid pathway genes expression in post-mortem brainsMetabolomics analysis shows secondary bile acids associated with cognitive declineGenome-scale metabolic networks of brain regions identify reactions linked to AD Baloni et al. use a systems biology approach to identify alterations in cholesterol and bile acid metabolism in Alzheimer disease (AD). Expression of alternative bile acid and neural cholesterol clearance pathway along with transporters of taurine and bile acids suggest the role of the gut-brain axis in AD.</description><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer's disease</subject><subject>bile acids</subject><subject>Bile Acids and Salts - metabolism</subject><subject>Brain - metabolism</subject><subject>Cholesterol - metabolism</subject><subject>Cognitive Dysfunction - metabolism</subject><subject>genome-scale metabolic models</subject><subject>Humans</subject><subject>Lipid Metabolism - physiology</subject><subject>Lipogenesis - physiology</subject><subject>Metabolic Networks and Pathways - physiology</subject><subject>metabolomics</subject><subject>Metabolomics - methods</subject><subject>transcriptional regulatory networks</subject><subject>Transcriptome - physiology</subject><subject>transcriptomics</subject><issn>2666-3791</issn><issn>2666-3791</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kElKBDEUhoMoKq0XcCG5QLcZqpIKiNDOggM4rEMqeWWnrUGSsrVdeQ2v50msolV04yqPvP__Qj6EtigZUULFznT0YkM1YoT1F4TybAmtMyHEkEtFl3_Na2gzxikhhKWUZpysojXOmUqyVK2j4gJakzelt_gS2ucmPOBxbcp59BFfwwxMGfG4bCGAw_u-BDy23uGbed1OoM-Y2uFvRKywr7v06wR8BeHj7T3iQx_BRNhAK0WHgs2vc4Dujo9uD06H51cnZwfj86FN0rQdJoXMpMqNBJZYRygRKresMLkQRDpjmFKSpTwRkEFqmSREckYyVfDC8oQ5PkB7C-7jU16Bs1C3wZT6MfjKhLlujNd_N7Wf6PtmpqVQNElUB2ALgA1NjAGKny4luhevp7oXr3vxeiG-K23_fvWn8q25C-wuAtD9feYh6Gg91BacD2Bb7Rr_H_8TzeqWzw</recordid><startdate>20201117</startdate><enddate>20201117</enddate><creator>Baloni, Priyanka</creator><creator>Funk, Cory C.</creator><creator>Yan, Jingwen</creator><creator>Yurkovich, James T.</creator><creator>Kueider-Paisley, Alexandra</creator><creator>Nho, Kwangsik</creator><creator>Heinken, Almut</creator><creator>Jia, Wei</creator><creator>Mahmoudiandehkordi, Siamak</creator><creator>Louie, Gregory</creator><creator>Saykin, Andrew J.</creator><creator>Arnold, Matthias</creator><creator>Kastenmüller, Gabi</creator><creator>Griffiths, William J.</creator><creator>Thiele, Ines</creator><creator>Kaddurah-Daouk, Rima</creator><creator>Kueider-Paisley, Alexandra</creator><creator>Louie, Gregory</creator><creator>Doraiswamy, P. 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Will ; Mahmoudiandehkhordi, Siamak ; Welsh-Balmer, Kathleen ; Plassman, Brenda ; Saykin, Andrew ; Nho, Kwangsik ; Kastenmüller, Gabi ; Arnold, Matthias ; Bhattacharyya, Sudeepa ; Han, Xianlin ; Baillie, Rebecca ; Fiehn, Oliver ; Barupal, Dinesh ; Meikle, Peter ; Mazmanian, Sarkis ; Kling, Mitchel ; Shaw, Leslie ; Trojanowski, John ; Toledo, Jon ; van Duijin, Cornelia ; Hankemier, Thomas ; Thiele, Ines ; Heinken, Almut ; Price, Nathan ; Funk, Cory ; Baloni, Priyanka ; Jia, Wei ; Wishart, David ; Brinton, Roberta ; Chang, Rui ; Farrer, Lindsay ; Au, Rhoda ; Qiu, Wendy ; Würtz, Peter ; Mangravite, Lara ; Krumsiek, Jan ; Newman, John ; Zhang, Bin ; Moreno, Herman ; Kaddurah-Daouk, Rima ; Price, Nathan D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-4f7879ba7e24cd01069bc2fab6607daa299725346e8e5c2700732089f3fc342d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer's disease</topic><topic>bile acids</topic><topic>Bile Acids and Salts - metabolism</topic><topic>Brain - metabolism</topic><topic>Cholesterol - metabolism</topic><topic>Cognitive Dysfunction - metabolism</topic><topic>genome-scale metabolic models</topic><topic>Humans</topic><topic>Lipid Metabolism - physiology</topic><topic>Lipogenesis - physiology</topic><topic>Metabolic Networks and Pathways - physiology</topic><topic>metabolomics</topic><topic>Metabolomics - methods</topic><topic>transcriptional regulatory networks</topic><topic>Transcriptome - physiology</topic><topic>transcriptomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baloni, Priyanka</creatorcontrib><creatorcontrib>Funk, Cory C.</creatorcontrib><creatorcontrib>Yan, Jingwen</creatorcontrib><creatorcontrib>Yurkovich, James T.</creatorcontrib><creatorcontrib>Kueider-Paisley, Alexandra</creatorcontrib><creatorcontrib>Nho, Kwangsik</creatorcontrib><creatorcontrib>Heinken, Almut</creatorcontrib><creatorcontrib>Jia, Wei</creatorcontrib><creatorcontrib>Mahmoudiandehkordi, Siamak</creatorcontrib><creatorcontrib>Louie, Gregory</creatorcontrib><creatorcontrib>Saykin, Andrew J.</creatorcontrib><creatorcontrib>Arnold, Matthias</creatorcontrib><creatorcontrib>Kastenmüller, Gabi</creatorcontrib><creatorcontrib>Griffiths, William J.</creatorcontrib><creatorcontrib>Thiele, Ines</creatorcontrib><creatorcontrib>Kaddurah-Daouk, Rima</creatorcontrib><creatorcontrib>Kueider-Paisley, Alexandra</creatorcontrib><creatorcontrib>Louie, Gregory</creatorcontrib><creatorcontrib>Doraiswamy, P. Murali</creatorcontrib><creatorcontrib>Blach, Colette</creatorcontrib><creatorcontrib>Moseley, Arthur</creatorcontrib><creatorcontrib>Thompson, J. Will</creatorcontrib><creatorcontrib>Mahmoudiandehkhordi, Siamak</creatorcontrib><creatorcontrib>Welsh-Balmer, Kathleen</creatorcontrib><creatorcontrib>Plassman, Brenda</creatorcontrib><creatorcontrib>Saykin, Andrew</creatorcontrib><creatorcontrib>Nho, Kwangsik</creatorcontrib><creatorcontrib>Kastenmüller, Gabi</creatorcontrib><creatorcontrib>Arnold, Matthias</creatorcontrib><creatorcontrib>Bhattacharyya, Sudeepa</creatorcontrib><creatorcontrib>Han, Xianlin</creatorcontrib><creatorcontrib>Baillie, Rebecca</creatorcontrib><creatorcontrib>Fiehn, Oliver</creatorcontrib><creatorcontrib>Barupal, Dinesh</creatorcontrib><creatorcontrib>Meikle, Peter</creatorcontrib><creatorcontrib>Mazmanian, Sarkis</creatorcontrib><creatorcontrib>Kling, Mitchel</creatorcontrib><creatorcontrib>Shaw, Leslie</creatorcontrib><creatorcontrib>Trojanowski, John</creatorcontrib><creatorcontrib>Toledo, Jon</creatorcontrib><creatorcontrib>van Duijin, Cornelia</creatorcontrib><creatorcontrib>Hankemier, Thomas</creatorcontrib><creatorcontrib>Thiele, Ines</creatorcontrib><creatorcontrib>Heinken, Almut</creatorcontrib><creatorcontrib>Price, Nathan</creatorcontrib><creatorcontrib>Funk, Cory</creatorcontrib><creatorcontrib>Baloni, Priyanka</creatorcontrib><creatorcontrib>Jia, Wei</creatorcontrib><creatorcontrib>Wishart, David</creatorcontrib><creatorcontrib>Brinton, Roberta</creatorcontrib><creatorcontrib>Chang, Rui</creatorcontrib><creatorcontrib>Farrer, Lindsay</creatorcontrib><creatorcontrib>Au, Rhoda</creatorcontrib><creatorcontrib>Qiu, Wendy</creatorcontrib><creatorcontrib>Würtz, Peter</creatorcontrib><creatorcontrib>Mangravite, Lara</creatorcontrib><creatorcontrib>Krumsiek, Jan</creatorcontrib><creatorcontrib>Newman, John</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Moreno, Herman</creatorcontrib><creatorcontrib>Kaddurah-Daouk, Rima</creatorcontrib><creatorcontrib>Price, Nathan D.</creatorcontrib><creatorcontrib>The Alzheimer’s Disease Metabolomics Consortium</creatorcontrib><creatorcontrib>Alzheimer’s Disease Metabolomics Consortium</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell reports. Medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baloni, Priyanka</au><au>Funk, Cory C.</au><au>Yan, Jingwen</au><au>Yurkovich, James T.</au><au>Kueider-Paisley, Alexandra</au><au>Nho, Kwangsik</au><au>Heinken, Almut</au><au>Jia, Wei</au><au>Mahmoudiandehkordi, Siamak</au><au>Louie, Gregory</au><au>Saykin, Andrew J.</au><au>Arnold, Matthias</au><au>Kastenmüller, Gabi</au><au>Griffiths, William J.</au><au>Thiele, Ines</au><au>Kaddurah-Daouk, Rima</au><au>Kueider-Paisley, Alexandra</au><au>Louie, Gregory</au><au>Doraiswamy, P. Murali</au><au>Blach, Colette</au><au>Moseley, Arthur</au><au>Thompson, J. Will</au><au>Mahmoudiandehkhordi, Siamak</au><au>Welsh-Balmer, Kathleen</au><au>Plassman, Brenda</au><au>Saykin, Andrew</au><au>Nho, Kwangsik</au><au>Kastenmüller, Gabi</au><au>Arnold, Matthias</au><au>Bhattacharyya, Sudeepa</au><au>Han, Xianlin</au><au>Baillie, Rebecca</au><au>Fiehn, Oliver</au><au>Barupal, Dinesh</au><au>Meikle, Peter</au><au>Mazmanian, Sarkis</au><au>Kling, Mitchel</au><au>Shaw, Leslie</au><au>Trojanowski, John</au><au>Toledo, Jon</au><au>van Duijin, Cornelia</au><au>Hankemier, Thomas</au><au>Thiele, Ines</au><au>Heinken, Almut</au><au>Price, Nathan</au><au>Funk, Cory</au><au>Baloni, Priyanka</au><au>Jia, Wei</au><au>Wishart, David</au><au>Brinton, Roberta</au><au>Chang, Rui</au><au>Farrer, Lindsay</au><au>Au, Rhoda</au><au>Qiu, Wendy</au><au>Würtz, Peter</au><au>Mangravite, Lara</au><au>Krumsiek, Jan</au><au>Newman, John</au><au>Zhang, Bin</au><au>Moreno, Herman</au><au>Kaddurah-Daouk, Rima</au><au>Price, Nathan D.</au><aucorp>The Alzheimer’s Disease Metabolomics Consortium</aucorp><aucorp>Alzheimer’s Disease Metabolomics Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer’s Disease</atitle><jtitle>Cell reports. Medicine</jtitle><addtitle>Cell Rep Med</addtitle><date>2020-11-17</date><risdate>2020</risdate><volume>1</volume><issue>8</issue><spage>100138</spage><pages>100138-</pages><artnum>100138</artnum><issn>2666-3791</issn><eissn>2666-3791</eissn><abstract>Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile acid synthesis pathway to be expressed in the brain. A targeted metabolomic analysis of primary and secondary bile acids measured from post-mortem brain samples of 111 individuals supports these results. Our metabolic network analysis suggests that taurine transport, bile acid synthesis, and cholesterol metabolism differ in AD and cognitively normal individuals. We also identify putative transcription factors regulating metabolic genes and influencing altered metabolism in AD. Intriguingly, some bile acids measured in brain tissue cannot be explained by the presence of enzymes responsible for their synthesis, suggesting that they may originate from the gut microbiome and are transported to the brain. These findings motivate further research into bile acid metabolism in AD to elucidate their possible connection to cognitive decline. [Display omitted] Altered cholesterol and bile acid metabolism linked to Alzheimer disease (AD)Evidence for alternative bile acid pathway genes expression in post-mortem brainsMetabolomics analysis shows secondary bile acids associated with cognitive declineGenome-scale metabolic networks of brain regions identify reactions linked to AD Baloni et al. use a systems biology approach to identify alterations in cholesterol and bile acid metabolism in Alzheimer disease (AD). Expression of alternative bile acid and neural cholesterol clearance pathway along with transporters of taurine and bile acids suggest the role of the gut-brain axis in AD.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33294859</pmid><doi>10.1016/j.xcrm.2020.100138</doi><oa>free_for_read</oa></addata></record>
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subjects Alzheimer Disease - metabolism
Alzheimer's disease
bile acids
Bile Acids and Salts - metabolism
Brain - metabolism
Cholesterol - metabolism
Cognitive Dysfunction - metabolism
genome-scale metabolic models
Humans
Lipid Metabolism - physiology
Lipogenesis - physiology
Metabolic Networks and Pathways - physiology
metabolomics
Metabolomics - methods
transcriptional regulatory networks
Transcriptome - physiology
transcriptomics
title Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer’s Disease
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