{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T11:28:14Z","timestamp":1794050894411,"version":"4.8.0"},"reference-count":75,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"41","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,10,11]]},"abstract":"<jats:p>\n            The intricate spatial configurations of brain networks offer essential insights into understanding the specific patterns of brain abnormalities and the underlying biological mechanisms associated with Alzheimer\u2019s disease (AD), normal aging, and other neurodegenerative disorders. This study investigated alterations in the topographical structure of the brain related to aging and neurodegenerative diseases by analyzing brain gradients derived from structural MRI data across multiple cohorts (\n            <jats:italic>n<\/jats:italic>\n            = 7323). The analysis identified distinct gradient patterns in AD, aging, and other neurodegenerative conditions. Gene enrichment analysis indicated that inorganic ion transmembrane transport was the most significant term in normal aging, while chemical synaptic transmission is a common enrichment term across various neurodegenerative diseases. Moreover, the findings show that each disorder exhibits unique dysfunctional neurophysiological characteristics. These insights are pivotal for elucidating the distinct biological mechanisms underlying AD, thereby enhancing our understanding of its unique clinical phenotypes in contrast to normal aging and other neurodegenerative disorders.\n          <\/jats:p>","DOI":"10.1126\/sciadv.ado8837","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T17:58:42Z","timestamp":1728669522000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":25,"title":["Macroscale connectome topographical structure reveals the biomechanisms of brain dysfunction in Alzheimer\u2019s disease"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5196-100X","authenticated-orcid":true,"given":"Kun","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4488-2135","authenticated-orcid":true,"given":"Dawei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Qilu Hospital of Shandong University, Jinan, China."},{"name":"Research Institute of Shandong University: Magnetic Field-free Medicine &amp; Functional Imaging, Jinan, China."},{"name":"Shandong Key Laboratory: Magnetic Field-free Medicine &amp; Functional Imaging (MF), Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pindong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, University of Chinese Academy of Sciences &amp; Brainnetome Center, Chinese Academy of Sciences, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8044-7667","authenticated-orcid":true,"given":"Yongbin","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3389-400X","authenticated-orcid":true,"given":"Liyun","family":"Tu","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8506-6096","authenticated-orcid":true,"given":"Yuqi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8052-065X","authenticated-orcid":true,"given":"Yi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxiang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Radiology, the Second Medical Centre, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Second Medical Centre, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0425-3921","authenticated-orcid":true,"given":"Jie","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengluan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, People\u2019s Hospital of Hangzhou Medical College, Zhejiang Provincial People's Hospital, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, People\u2019s Hospital of Hangzhou Medical College, Zhejiang Provincial People's Hospital, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China."},{"name":"National Clinical Research Center for Geriatric Disorders, Beijing, China."},{"name":"Center of Alzheimer\u2019s Disease, Beijing Institute for Brain Disorders, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Second Medical Centre, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1862-3121","authenticated-orcid":true,"given":"Yong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing, China."},{"name":"School of Artificial Intelligence, University of Chinese Academy of Sciences &amp; Brainnetome Center, Chinese Academy of Sciences, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.04.004"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2017.17050529"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01382-x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12323"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235381"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3465"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3214"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1608282113"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb3417"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25162-w"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2017.11.002"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/121.6.1013"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23111-1"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.117846"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbaa016"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02572-6"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab151"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.010"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.01.017"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.02.036"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000284"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14518-3"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.36652"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06098-1"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01376-7"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109582"},{"key":"e_1_3_2_28_2","first-page":"783","article-title":"Regional radiomics similarity networks (R2SNs) in the human brain: Reproducibility, small-world properties and a biological basis","volume":"5","author":"Zhao K.","year":"2021","unstructured":"K. Zhao, Q. Zheng, T. Che, M. Dyrba, Q. Li, Y. Ding, Y. Zheng, Y. Liu, S. Li, Regional radiomics similarity networks (R2SNs) in the human brain: Reproducibility, small-world properties and a biological basis. Netw. Neurosci. 5, 783\u2013797 (2021).","journal-title":"Netw. Neurosci."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102276"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01519-5"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2024448118"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.118987"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00338.2011"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-00967-1"},{"key":"e_1_3_2_35_2","first-page":"436","article-title":"Brain-wide analysis of functional connectivity in first-episode and chronic stages of schizophrenia","volume":"43","author":"Li T.","year":"2017","unstructured":"T. Li, Q. Wang, J. Zhang, E. T. Rolls, W. Yang, L. Palaniyappan, L. Zhang, W. Cheng, Y. Yao, Z. Liu, X. Gong, Q. Luo, Y. Tang, T. J. Crow, M. R. Broome, K. Xu, C. Li, J. Wang, Z. Liu, G. Lu, F. Wang, J. Feng, Brain-wide analysis of functional connectivity in first-episode and chronic stages of schizophrenia. Schizophr. Bull. 43, 436\u2013448 (2017).","journal-title":"Schizophr. Bull."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww143"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2020.04.003"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0793-8"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44220-023-00110-3"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21943-5"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0483-4"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101208"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.11.039"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba5933"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23091"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023832305702"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr066"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1089\/brain.2014.0236"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1921475117"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab375"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2583"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.05.004"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11062-019-09823-7"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0721-9"},{"key":"e_1_3_2_55_2","first-page":"563481","article-title":"Neurodegenerative diseases: Multifactorial conformational diseases and their therapeutic interventions","volume":"2013","author":"Sheikh S.","year":"2013","unstructured":"S. Sheikh, Safia, E. Haque, S. S. Mir, Neurodegenerative diseases: Multifactorial conformational diseases and their therapeutic interventions. J. Neurodegener. Dis. 2013, 563481 (2013).","journal-title":"J. Neurodegener. Dis."},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.05.011"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00069-6"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002058"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23188-8"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac102"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12306"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adl2675"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14187"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx327"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-023-00378-6"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan2742"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10449-w"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw157"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202104538"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500334102"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-020-0493-8"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-021-01004-8"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcm.2016.02.012"},{"key":"e_1_3_2_74_2","first-page":"171","article-title":"On the combination of independent tests","volume":"3","author":"Liptak T.","year":"1958","unstructured":"T. Liptak, On the combination of independent tests. Magyar Tud. Akad. Mat. Kutat\u00f3 Int. K\u00f6zl. 3, 171\u2013197 (1958).","journal-title":"Magyar Tud. Akad. Mat. Kutat\u00f3 Int. K\u00f6zl."},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.09.005"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.ado8837","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T17:58:44Z","timestamp":1728669524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.ado8837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,11]]},"references-count":75,"journal-issue":{"issue":"41","published-print":{"date-parts":[[2024,10,11]]}},"alternative-id":["10.1126\/sciadv.ado8837"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.ado8837","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,11]]},"assertion":[{"value":"2024-02-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eado8837"}}