{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:07:02Z","timestamp":1789560422778,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801752"],"award-info":[{"award-number":["81801752"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571345"],"award-info":[{"award-number":["81571345"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8217052097"],"award-info":[{"award-number":["8217052097"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201583"],"award-info":[{"award-number":["82201583"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>We investigated the associations of longitudinal synaptic loss and cognitive decline with tau burden and plasma biomarkers in Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Twenty cognitively impaired (CI) individuals and 16 healthy controls (HC) underwent cognitive and plasma biomarker assessments, amyloid positron emission tomography (PET), tau PET, and synaptic density PET; after 1 year, tau and synaptic density PET were repeated. The relationships among tau burden, plasma biomarkers, synaptic density, and cognition were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The CI group had more longitudinal synapse loss and tau deposition than HCs. Longitudinal synaptic loss was positively associated with longitudinal cognitive decline, negatively with longitudinal tau deposition. Plasma glial fibrillary acidic protein (GFAP) mediates the relationship between longitudinal tau deposition and longitudinal synaptic loss. Tau burden, plasma phosphorylated tau181, and GFAP could predict longitudinal synaptic loss and cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The CI group had more longitudinal synapse loss and tau burden increases than HCs. Tau pathology and plasma GFAP could predict longitudinal synapse loss and cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Cognitively impaired individuals had more longitudinal synapse loss in the medial temporal lobe, and increased tau burden in the widespread neocortex than healthy controls.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The longitudinal change of synaptic density was negatively associated with the longitudinal change of tau burden, and positively associated with longitudinal cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma glial fibrillary acidic protein (GFAP) mediates the relationship between longitudinal tau deposition and longitudinal synaptic loss.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tau burden, plasma phosphorylated tau181, and GFAP could predict longitudinal synaptic loss and cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70333","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T02:39:08Z","timestamp":1748399948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Prediction of longitudinal synaptic loss in Alzheimer's disease using tau PET and plasma biomarkers"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4338-2873","authenticated-orcid":false,"given":"Jie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine &amp; PET Center Huashan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine &amp; PET Center Huashan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Shanghai East Hospital, Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"You","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Shanghai East Hospital, Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine &amp; PET Center Huashan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxie","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine &amp; PET Center Huashan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyun","family":"Huang","sequence":"additional","affiliation":[{"name":"PET Center Department of Radiology and Biomedical Imaging Yale University School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Franzmeier","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research (ISD) LMU University Hospital, Ludwig\u2010Maximilians\u2010University (LMU) Munich Germany"},{"name":"Institute of Neuroscience and Physiology Munich Cluster for Systems Neurology (SyNergy) Munich Germany"},{"name":"Department of Psychiatry and Neurochemistry University of Gothenburg, The Sahlgrenska Academy, Institute of Neuroscience and Physiology Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sch\u00f6ll","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry University of Gothenburg, The Sahlgrenska Academy, Institute of Neuroscience and Physiology Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering Shenzhen Bay Laboratory Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Shanghai East Hospital, Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihui","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine &amp; PET Center Huashan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqing","family":"Ni","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering Institute for Regenerative Medicine University of Zurich &amp; ETH Zurich, Zurich; Department of Nuclear Medicine, Inselspital Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binyin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2667-281X","authenticated-orcid":false,"given":"Fang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine &amp; PET Center Huashan Hospital, Fudan University Shanghai China"},{"name":"MOE Frontiers Center for Brain Science Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2003.09.001"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/neur.1996.0056"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01465-2"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.120.249144"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12097"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01672-x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01672-x"},{"key":"e_1_2_8_10_1","article-title":"Longitudinal synaptic loss versus tau Braak staging in amnestic mild cognitive impairment","author":"Greet V","year":"2024","journal-title":"Alzheimers Dement"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/tnsci-2015-0023"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2021.11.004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.233019"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-019-01367-w"},{"issue":"1","key":"e_1_2_8_15_1","first-page":"871","article-title":"Synaptic biomarkers in CSF aid in diagnosis, correlate with cognition and predict progression in MCI and Alzheimer's disease","volume":"5","author":"Douglas G","year":"2019","journal-title":"Alzheimers Dement"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00749-z"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.0765"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-024-00420-1"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2023.49"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01385-z"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-221166"},{"key":"e_1_2_8_22_1","first-page":"28","article-title":"Progression and predictors of mild cognitive impairment in Chinese elderly: a prospective follow\u2010up in the Shanghai Aging Study","volume":"4","author":"Ding D","year":"2016","journal-title":"Alzheimers Dement"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70004"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/JGP.0b013e31819431d5"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13775"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47897-y"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/2211068215589580"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.832700"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13817"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02501-z"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X241230733"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0978"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-023-10366-z"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-025-07080-x"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.2018180160"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.10163"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-90"},{"issue":"5","key":"e_1_2_8_39_1","first-page":"e545","article-title":"In vivo synaptic density loss is related to tau deposition in amnestic mild cognitive impairment","volume":"95","author":"Heleen V","year":"2020","journal-title":"Neurology"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.09.012"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.11.030"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4328"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15295"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-023-01212-x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12239"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abi8593"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902301116"},{"issue":"3","key":"e_1_2_8_48_1","first-page":"157","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?","volume":"17","author":"Fangda L","year":"2020","journal-title":"Nat Rev Neurol"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae234"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02853-3"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(02)00358-6"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.0718"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab223"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12582"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70333","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70333","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70333","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:34:02Z","timestamp":1789558442000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":53,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/alz.70333"],"URL":"https:\/\/doi.org\/10.1002\/alz.70333","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"2025-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70333"}}