{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:10:07Z","timestamp":1782958207012,"version":"3.54.5"},"reference-count":69,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1 AG061729"],"award-info":[{"award-number":["RF1 AG061729"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1 AG061872"],"award-info":[{"award-number":["RF1 AG061872"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["T32AG021890"],"award-info":[{"award-number":["T32AG021890"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AG013319"],"award-info":[{"award-number":["P30 AG013319"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AG044271"],"award-info":[{"award-number":["P30 AG044271"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AG066546"],"award-info":[{"award-number":["P30 AG066546"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Despite being a brain disorder, Alzheimer's disease (AD) is often accompanied by peripheral organ dysregulations (e.g., loss of bladder control in late\u2010stage AD), which highly rely on spinal cord coordination. However, the causal factor(s) for peripheral organ dysregulation in AD remain elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The central nervous system (CNS) is enriched in lipids. We applied quantitative shotgun lipidomics to determine lipid profiles of human AD spinal cord tissues. Additionally, a CNS sulfatide (ST)\u2010deficient mouse model was used to study the lipidome, transcriptome and peripheral organ phenotypes of ST loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed marked myelin lipid reduction in the spinal cord of AD subjects versus cognitively normal individuals. Among which, levels of ST, a myelin\u2010enriched lipid class, were strongly and negatively associated with the severity of AD. A CNS myelin\u2010specific ST\u2010deficient mouse model was used to further identify the causes and consequences of spinal cord lipidome changes. Interestingly, ST deficiency led to spinal cord lipidome and transcriptome profiles highly resembling those observed in AD, characterized by decline of multiple myelin\u2010enriched lipid classes and enhanced inflammatory responses, respectively. These changes significantly disrupted spinal cord function and led to substantial enlargement of urinary bladder in ST\u2010deficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study identified CNS ST deficiency as a causal factor for AD\u2010like lipid dysregulation, inflammation response and ultimately the development of bladder disorders. Targeting to maintain ST levels may serve as a promising strategy for the prevention and treatment of AD\u2010related peripheral disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1332","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T18:25:19Z","timestamp":1689963919000},"source":"Crossref","is-referenced-by-count":11,"title":["Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3786-8770","authenticated-orcid":false,"given":"Sijia","family":"He","sequence":"first","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixia","family":"Pan","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Palavicini","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San Antonio Texas USA"},{"name":"Division of Diabetes Department of Medicine University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Wang","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anindita","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah","family":"Barannikov","sequence":"additional","affiliation":[{"name":"Department of Pathology Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin F.","family":"Bieniek","sequence":"additional","affiliation":[{"name":"Department of Pathology Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Dupree","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology Virginia Commonwealth University Richmond Virginia USA"},{"name":"Research Division McGuire Veterans Affairs Medical Center Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlin","family":"Han","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San Antonio Texas USA"},{"name":"Division of Diabetes Department of Medicine University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2008.02503.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12877-020-01744-z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hct103"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.777819"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00120-003-0457-6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1533317516680900"},{"issue":"6","key":"e_1_2_9_8_1","first-page":"16","article-title":"Environmental effects on incontinence problems in Alzheimer's disease patients","volume":"6","author":"Kevan H","year":"1991","journal-title":"Am J Alzheimer's Care Related Dis Res"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00006"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci9070168"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.20883"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-121864"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/60.5.483"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-122323"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0188218"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41393-017-0009-3"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2217\/17460875.2.4.403"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48059-7"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00488-7"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00332.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00997.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310483"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11051431"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010233"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glt136"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu208"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13738"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac900241u"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.21492"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005901"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2018.06.014"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-03-00994.2003"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0515-3"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-009-8092-x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6221-11.2012"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63247-0.00005-5"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10154"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00417"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi062152y"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(03)00506-8"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2022.151244"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25125-1"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700400-JLR200"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa246"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3916"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-00402-7"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00598"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01024-z"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0358-2"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199907000-00008"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011603916962"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15488"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2012-110629"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-017-1304-x"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041505"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05439-w"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.02.025"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1195-2"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611056200"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2018.76863"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056972"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.2147\/RRU.S29644"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1308\/rcsann.2018.0002"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.73.2.154"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.049"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1596"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01022-0"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04473-1"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00436-5"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.1332","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T23:44:44Z","timestamp":1692315884000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.1332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7]]},"references-count":69,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/ctm2.1332"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.1332","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7]]},"article-number":"e1332"}}