{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:53:20Z","timestamp":1790974400379,"version":"4.1.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100007390","name":"Instituto Nacional de Ci\u00eancia e Tecnologia Centro de Estudos das Adapta\u00e7\u00f5es da Biota Aqu\u00e1tica da Amaz\u00f4nia","doi-asserted-by":"publisher","award":["2022ZD0211800"],"award-info":[{"award-number":["2022ZD0211800"]}],"id":[{"id":"10.13039\/501100007390","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1007\/s00259-026-08067-y","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T01:37:57Z","timestamp":1784252277000},"page":"7460-7475","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In vivo multimodal PET\/MRI imaging and plasma biomarkers implicate glymphatic dysfunction linking neuroinflammation to tau pathology in the early Alzheimer\u2019s disease continuum"],"prefix":"10.1007","volume":"53","author":[{"given":"Xinru","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaichen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotian","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haocheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyu","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengyan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkang","family":"Gai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-0290","authenticated-orcid":false,"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"issue":"8","key":"8067_CR1","doi-asserted-by":"publisher","first-page":"5143","DOI":"10.1002\/alz.13859","volume":"20","author":"CR Jack Jr","year":"2024","unstructured":"Jack CR Jr., Andrews JS, Beach TG, Buracchio T, Dunn B, Graf A, Hansson O, Ho C, Jagust W, McDade E, et al. Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup. Alzheimer\u2019s Dement J Alzheimer\u2019s Assoc. 2024;20(8):5143\u201369. https:\/\/doi.org\/10.1002\/alz.13859.","journal-title":"Alzheimer\u2019s Dement J Alzheimer\u2019s Assoc"},{"key":"8067_CR2","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.neulet.2019.04.022","volume":"705","author":"NN Naseri","year":"2019","unstructured":"Naseri NN, Wang H, Guo J, Sharma M, Luo W. The complexity of tau in Alzheimer\u2019s disease. Neurosci Lett. 2019;705:183\u201394. https:\/\/doi.org\/10.1016\/j.neulet.2019.04.022.","journal-title":"Neurosci Lett"},{"issue":"6","key":"8067_CR3","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1038\/nn.4017","volume":"18","author":"K Herrup","year":"2015","unstructured":"Herrup K. The case for rejecting the amyloid cascade hypothesis. Nat Neurosci. 2015;18(6):794\u20139. https:\/\/doi.org\/10.1038\/nn.4017.","journal-title":"Nat Neurosci"},{"issue":"2","key":"8067_CR4","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.molmed.2018.11.006","volume":"25","author":"SF Carter","year":"2019","unstructured":"Carter SF, Herholz K, Rosa-Neto P, Pellerin L, Nordberg A, Zimmer ER. Astrocyte Biomarkers in Alzheimer\u2019s Disease. Trends Mol Med. 2019;25(2):77\u201395. https:\/\/doi.org\/10.1016\/j.molmed.2018.11.006.","journal-title":"Trends Mol Med"},{"issue":"10","key":"8067_CR5","doi-asserted-by":"publisher","first-page":"e70709","DOI":"10.1002\/alz.70709","volume":"21","author":"J Ding","year":"2025","unstructured":"Ding J, Zhao C, Hao X, Jiao H. Glymphatic and meningeal lymphatic dysfunction in Alzheimer\u2019s disease: Mechanisms and therapeutic perspectives. Alzheimers Dement. 2025;21(10):e70709. https:\/\/doi.org\/10.1002\/alz.70709.","journal-title":"Alzheimers Dement"},{"issue":"147","key":"8067_CR6","doi-asserted-by":"publisher","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","volume":"4","author":"JJ Iliff","year":"2012","unstructured":"Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2. Sci Transl Med. 2012;4(147):147ra111. https:\/\/doi.org\/10.1126\/scitranslmed.3003748.","journal-title":"Sci Transl Med"},{"issue":"11","key":"8067_CR7","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/s1474-4422(18)30318-1","volume":"17","author":"MK Rasmussen","year":"2018","unstructured":"Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol. 2018;17(11):1016\u201324. https:\/\/doi.org\/10.1016\/s1474-4422(18)30318-1.","journal-title":"Lancet Neurol"},{"issue":"12","key":"8067_CR8","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.4103\/1673-5374.391312","volume":"19","author":"K Zou","year":"2024","unstructured":"Zou K, Deng Q, Zhang H, Huang C. Glymphatic system: a gateway for neuroinflammation. Neural regeneration Res. 2024;19(12):2661\u201372. https:\/\/doi.org\/10.4103\/1673-5374.391312.","journal-title":"Neural regeneration Res"},{"key":"8067_CR9","doi-asserted-by":"publisher","unstructured":"Cai Y, Zhang Y, Leng S, Ma Y, Jiang Q, Wen Q, Ju S, Hu J. The relationship between inflammation, impaired glymphatic system, and neurodegenerative disorders: A vicious cycle. Neurobiol Dis 2024, 192:106426. https:\/\/doi.org\/10.1016\/j.nbd.2024.106426","DOI":"10.1016\/j.nbd.2024.106426"},{"key":"8067_CR10","doi-asserted-by":"publisher","unstructured":"Szlufik S, Kope\u0107 K, Szleszkowski S, Koziorowski D. Glymphatic system pathology and neuroinflammation as two risk factors of neurodegeneration. Cells. 2024;13(3). https:\/\/doi.org\/10.3390\/cells13030286.","DOI":"10.3390\/cells13030286"},{"issue":"7","key":"8067_CR11","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1038\/s41591-023-02380-x","volume":"29","author":"B Bellaver","year":"2023","unstructured":"Bellaver B, Povala G, Ferreira PCL, Ferrari-Souza JP, Leffa DT, Lussier FZ, Benedet AL, Ashton NJ, Triana-Baltzer G, Kolb HC, et al. Astrocyte reactivity influences amyloid-\u03b2 effects on tau pathology in preclinical Alzheimer\u2019s disease. Nat Med. 2023;29(7):1775\u201381. https:\/\/doi.org\/10.1038\/s41591-023-02380-x.","journal-title":"Nat Med"},{"issue":"9","key":"8067_CR12","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1038\/s41591-021-01456-w","volume":"27","author":"TA Pascoal","year":"2021","unstructured":"Pascoal TA, Benedet AL, Ashton NJ, Kang MS, Therriault J, Chamoun M, Savard M, Lussier FZ, Tissot C, Karikari TK, et al. Microglial activation and tau propagate jointly across Braak stages. Nat Med. 2021;27(9):1592\u20139. https:\/\/doi.org\/10.1038\/s41591-021-01456-w.","journal-title":"Nat Med"},{"key":"8067_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-02103-0","author":"JP Ferrari-Souza","year":"2025","unstructured":"Ferrari-Souza JP, Povala G, Rahmouni N, Bellaver B, Ferreira PCL, De Bastiani MA, Leffa DT, Lussier FZ, Aguzzoli CS, Brum WS, et al. Microglia modulate A\u03b2-dependent astrocyte reactivity in Alzheimer\u2019s disease. Nat Neurosci. 2025. https:\/\/doi.org\/10.1038\/s41593-025-02103-0.","journal-title":"Nat Neurosci"},{"issue":"4","key":"8067_CR14","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1007\/s11604-017-0617-z","volume":"35","author":"T Taoka","year":"2017","unstructured":"Taoka T, Masutani Y, Kawai H, Nakane T, Matsuoka K, Yasuno F, Kishimoto T, Naganawa S. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer\u2019s disease cases. Japanese J Radiol. 2017;35(4):172\u20138. https:\/\/doi.org\/10.1007\/s11604-017-0617-z.","journal-title":"Japanese J Radiol"},{"key":"8067_CR15","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14149","author":"Y Li","year":"2024","unstructured":"Li Y, Wang L, Zhong J, Xu H, Han Y, Zuo C, Jiang J. Impaired glymphatic function as a biomarker for subjective cognitive decline: An exploratory dual cohort study. Alzheimer\u2019s Dement. 2024. https:\/\/doi.org\/10.1002\/alz.14149.","journal-title":"Alzheimer\u2019s Dement"},{"key":"8067_CR16","doi-asserted-by":"publisher","unstructured":"Bao C, Luo H, Wang J, Liu X, Li Y, Yang J, Chen C, Yang R, Ba W, Lian X et al. Poor glymphatic function is associated with mild cognitive impairment and its progression to Alzheimer\u2019s disease: A DTI-ALPS study. J Prev Alzheimer\u2019s disease 2025:100156. https:\/\/doi.org\/10.1016\/j.tjpad.2025.100156","DOI":"10.1016\/j.tjpad.2025.100156"},{"issue":"11","key":"8067_CR17","doi-asserted-by":"publisher","first-page":"2602","DOI":"10.1007\/s00259-020-04772-4","volume":"47","author":"T Rodr\u00edguez-Chinchilla","year":"2020","unstructured":"Rodr\u00edguez-Chinchilla T, Quiroga-Varela A, Molinet-Dronda F, Belloso-Iguerategui A, Merino-Galan L, Jimenez-Urbieta H, Gago B, Rodriguez-Oroz MC. [(18)F]-DPA-714 PET as a specific in vivo marker of early microglial activation in a rat model of progressive dopaminergic degeneration. Eur J Nucl Med Mol Imaging. 2020;47(11):2602\u201312. https:\/\/doi.org\/10.1007\/s00259-020-04772-4.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"8067_CR18","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.pharmthera.2018.09.003","volume":"194","author":"TR Guilarte","year":"2019","unstructured":"Guilarte TR. TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a way forward. Pharmacol Ther. 2019;194:44\u201358. https:\/\/doi.org\/10.1016\/j.pharmthera.2018.09.003.","journal-title":"Pharmacol Ther"},{"issue":"7","key":"8067_CR19","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1001\/jamaneurol.2020.0528","volume":"77","author":"AS Fleisher","year":"2020","unstructured":"Fleisher AS, Pontecorvo MJ, Devous MD, Sr., Lu M, Arora AK, Truocchio SP, Aldea P, Flitter M, Locascio T, Devine M, et al. Positron Emission tomography imaging With [18F]flortaucipir and postmortem assessment of Alzheimer disease neuropathologic changes. JAMA Neurol. 2020;77(7):829\u201339. https:\/\/doi.org\/10.1001\/jamaneurol.2020.0528.","journal-title":"JAMA Neurol"},{"issue":"1","key":"8067_CR20","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/s13195-023-01340-4","volume":"15","author":"Z Yang","year":"2023","unstructured":"Yang Z, Sreenivasan K, Toledano Strom EN, Osse AML, Pasia LG, Cosme CG, Mugosa MRN, Chevalier EL, Ritter A, Miller JB, et al. Clinical and biological relevance of glial fibrillary acidic protein in Alzheimer\u2019s disease. Alzheimers Res Ther. 2023;15(1):190. https:\/\/doi.org\/10.1186\/s13195-023-01340-4.","journal-title":"Alzheimers Res Ther"},{"issue":"12","key":"8067_CR21","doi-asserted-by":"publisher","first-page":"4094","DOI":"10.1093\/brain\/awae211","volume":"147","author":"DE Peretti","year":"2024","unstructured":"Peretti DE, Boccalini C, Ribaldi F, Scheffler M, Marizzoni M, Ashton NJ, Zetterberg H, Blennow K, Frisoni GB, Garibotto V. Association of glial fibrillary acid protein, Alzheimer\u2019s disease pathology and cognitive decline. Brain. 2024;147(12):4094\u2013104. https:\/\/doi.org\/10.1093\/brain\/awae211.","journal-title":"Brain"},{"issue":"3","key":"8067_CR22","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1212\/WNL.0b013e3181cb3e25","volume":"74","author":"RC Petersen","year":"2010","unstructured":"Petersen RC, Aisen PS, Beckett LA, Donohue MC, Gamst AC, Harvey DJ, Jack CR Jr., Jagust WJ, Shaw LM, Toga AW, et al. Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology. 2010;74(3):201\u20139. https:\/\/doi.org\/10.1212\/WNL.0b013e3181cb3e25.","journal-title":"Neurology"},{"issue":"4","key":"8067_CR23","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr","year":"2018","unstructured":"Jack CR Jr., Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease. Alzheimer\u2019s Dement J Alzheimer\u2019s Assoc. 2018;14(4):535\u201362. https:\/\/doi.org\/10.1016\/j.jalz.2018.02.018.","journal-title":"Alzheimer\u2019s Dement J Alzheimer\u2019s Assoc"},{"key":"8067_CR24","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.neuroimage.2016.02.042","volume":"132","author":"DN Greve","year":"2016","unstructured":"Greve DN, Salat DH, Bowen SL, Izquierdo-Garcia D, Schultz AP, Catana C, Becker JA, Svarer C, Knudsen GM, Sperling RA, et al. Different partial volume correction methods lead to different conclusions: An (18)F-FDG-PET study of aging. NeuroImage. 2016;132:334\u201343. https:\/\/doi.org\/10.1016\/j.neuroimage.2016.02.042.","journal-title":"NeuroImage"},{"issue":"Pt 4","key":"8067_CR25","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1093\/brain\/aww017","volume":"139","author":"L Hamelin","year":"2016","unstructured":"Hamelin L, Lagarde J, Doroth\u00e9e G, Leroy C, Labit M, Comley RA, de Souza LC, Corne H, Dauphinot L, Bertoux M, et al. Early and protective microglial activation in Alzheimer\u2019s disease: a prospective study using 18F-DPA-714 PET imaging. Brain. 2016;139(Pt 4):1252\u201364. https:\/\/doi.org\/10.1093\/brain\/aww017.","journal-title":"Brain"},{"issue":"6","key":"8067_CR26","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1093\/brain\/awy079","volume":"141","author":"L Hamelin","year":"2018","unstructured":"Hamelin L, Lagarde J, Doroth\u00e9e G, Potier MC, Corlier F, Kuhnast B, Caill\u00e9 F, Dubois B, Fillon L, Chupin M, et al. Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer\u2019s disease. Brain. 2018;141(6):1855\u201370. https:\/\/doi.org\/10.1093\/brain\/awy079.","journal-title":"Brain"},{"issue":"2","key":"8067_CR27","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1007\/s00259-023-06446-3","volume":"51","author":"M Zhang","year":"2024","unstructured":"Zhang M, Qian XH, Hu J, Zhang Y, Lin X, Hai W, Shi K, Jiang X, Li Y, Tang HD, et al. Integrating TSPO PET imaging and transcriptomics to unveil the role of neuroinflammation and amyloid-beta deposition in Alzheimer\u2019s disease. Eur J Nucl Med Mol Imaging. 2024;51(2):455\u201367. https:\/\/doi.org\/10.1007\/s00259-023-06446-3.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"8067_CR28","doi-asserted-by":"crossref","unstructured":"Rosseel YJJoSS: lavaan: An R Package for Structural Equation Modeling. 2012, 48.","DOI":"10.18637\/jss.v048.i02"},{"issue":"1","key":"8067_CR29","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/s41593-025-02103-0","volume":"29","author":"JP Ferrari-Souza","year":"2026","unstructured":"Ferrari-Souza JP, Povala G, Rahmouni N, Bellaver B, Ferreira PCL, De Bastiani MA, Leffa DT, Lussier FZ, Aguzzoli CS, Brum WS, et al. Microglia modulate A\u03b2-dependent astrocyte reactivity in Alzheimer\u2019s disease. Nat Neurosci. 2026;29(1):81\u20137. https:\/\/doi.org\/10.1038\/s41593-025-02103-0.","journal-title":"Nat Neurosci"},{"issue":"1","key":"8067_CR30","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1186\/s12974-018-1309-z","volume":"15","author":"SC Hopp","year":"2018","unstructured":"Hopp SC, Lin Y, Oakley D, Roe AD, DeVos SL, Hanlon D, Hyman BT. The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer\u2019s disease. J Neuroinflamm. 2018;15(1):269. https:\/\/doi.org\/10.1186\/s12974-018-1309-z.","journal-title":"J Neuroinflamm"},{"issue":"1","key":"8067_CR31","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1093\/brain\/awae234","volume":"148","author":"J Appleton","year":"2025","unstructured":"Appleton J, Finn Q, Zanotti-Fregonara P, Yu M, Faridar A, Nakawah MO, Zarate C, Carrillo MC, Dickerson BC, Rabinovici GD, et al. Brain inflammation co-localizes highly with tau in mild cognitive impairment due to early-onset Alzheimer\u2019s disease. Brain. 2025;148(1):119\u201332. https:\/\/doi.org\/10.1093\/brain\/awae234.","journal-title":"Brain"},{"key":"8067_CR32","doi-asserted-by":"publisher","unstructured":"Lee WJ, Brown JA, Kim HR, La Joie R, Cho H, Lyoo CH, Rabinovici GD, Seong JK, Seeley WW. Regional A\u03b2-tau interactions promote onset and acceleration of Alzheimer\u2019s disease tau spreading. Neuron 2022, 110(12):1932\u20131943.e1935. https:\/\/doi.org\/10.1016\/j.neuron.2022.03.034","DOI":"10.1016\/j.neuron.2022.03.034"},{"issue":"1","key":"8067_CR33","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13024-024-00750-8","volume":"19","author":"T Guo","year":"2024","unstructured":"Guo T, Li A, Sun P, He Z, Cai Y, Lan G, Liu L, Li J, Yang J, Zhu Y, et al. Astrocyte reactivity is associated with tau tangle load and cortical thinning in Alzheimer\u2019s disease. Mol neurodegeneration. 2024;19(1):58. https:\/\/doi.org\/10.1186\/s13024-024-00750-8.","journal-title":"Mol neurodegeneration"},{"issue":"2","key":"8067_CR34","doi-asserted-by":"publisher","first-page":"e233019","DOI":"10.1148\/radiol.233019","volume":"313","author":"J Wu","year":"2024","unstructured":"Wu J, Li B, Wang J, Huang Q, Chen X, You Z, He K, Guo Q, Li S, Huang YH, et al. Plasma glial fibrillary acid protein and phosphorated Tau 181 association with presynaptic density-dependent tau pathology at (18)F-SynVesT-1 Brain PET imaging. Radiology. 2024;313(2):e233019. https:\/\/doi.org\/10.1148\/radiol.233019.","journal-title":"Radiology"},{"issue":"3","key":"8067_CR35","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","volume":"17","author":"F Leng","year":"2021","unstructured":"Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021;17(3):157\u201372. https:\/\/doi.org\/10.1038\/s41582-020-00435-y.","journal-title":"Nat Rev Neurol"},{"issue":"2","key":"8067_CR36","doi-asserted-by":"publisher","first-page":"71","DOI":"10.12779\/dnd.2022.21.2.71","volume":"21","author":"H Lee","year":"2022","unstructured":"Lee H, Noh Y, Kim WR, Seo HE, Park HM. Translocator Protein (18\u00a0kDa) Polymorphism (rs6971) in the Korean Population. Dement neurocognitive disorders. 2022;21(2):71\u20138. https:\/\/doi.org\/10.12779\/dnd.2022.21.2.71.","journal-title":"Dement neurocognitive disorders"},{"issue":"8","key":"8067_CR37","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.1093\/brain\/awaa179","volume":"143","author":"IF Harrison","year":"2020","unstructured":"Harrison IF, Ismail O, Machhada A, Colgan N, Ohene Y, Nahavandi P, Ahmed Z, Fisher A, Meftah S, Murray TK, et al. Impaired glymphatic function and clearance of tau in an Alzheimer\u2019s disease model. Brain. 2020;143(8):2576\u201393. https:\/\/doi.org\/10.1093\/brain\/awaa179.","journal-title":"Brain"},{"key":"8067_CR38","doi-asserted-by":"publisher","unstructured":"Ishida K, Yamada K, Nishiyama R, Hashimoto T, Nishida I, Abe Y, Yasui M, Iwatsubo T. Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration. J Exp Med. 2022;219(3). https:\/\/doi.org\/10.1084\/jem.20211275.","DOI":"10.1084\/jem.20211275"},{"issue":"1","key":"8067_CR39","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1002\/ana.26516","volume":"93","author":"JL Hsu","year":"2023","unstructured":"Hsu JL, Wei YC, Toh CH, Hsiao IT, Lin KJ, Yen TC, Liao MF, Ro LS. Magnetic resonance images implicate that glymphatic alterations mediate cognitive dysfunction in Alzheimer disease. Ann Neurol. 2023;93(1):164\u201374. https:\/\/doi.org\/10.1002\/ana.26516.","journal-title":"Ann Neurol"},{"key":"8067_CR40","doi-asserted-by":"publisher","first-page":"120524","DOI":"10.1016\/j.neuroimage.2024.120524","volume":"288","author":"L Xie","year":"2024","unstructured":"Xie L, Zhang Y, Hong H, Xu S, Cui L, Wang S, Li J, Liu L, Lin M, Luo X, et al. Higher intracranial arterial pulsatility is associated with presumed imaging markers of the glymphatic system: An explorative study. NeuroImage. 2024;288:120524. https:\/\/doi.org\/10.1016\/j.neuroimage.2024.120524.","journal-title":"NeuroImage"},{"key":"8067_CR41","doi-asserted-by":"publisher","unstructured":"Zhou C, Jiang X, Guan X, Guo T, Wu J, Wu H, Wu C, Chen J, Wen J, Tan S, et al. Glymphatic system dysfunction and risk of clinical milestones in patients with Parkinson disease. Eur J Neurol. 2024;e16521. https:\/\/doi.org\/10.1111\/ene.16521.","DOI":"10.1111\/ene.16521"},{"key":"8067_CR42","doi-asserted-by":"publisher","unstructured":"Bae YJ, Kim J-M, Choi BS, Ryoo N, Song YS, Nam Y, Yoon I-Y, Cho SJ, Kim JH. Altered brain glymphatic flow at diffusion-tensor MRI in rapid eye movement sleep behavior disorder. Radiology. 2023;307(5). https:\/\/doi.org\/10.1148\/radiol.221848.","DOI":"10.1148\/radiol.221848"},{"key":"8067_CR43","doi-asserted-by":"publisher","unstructured":"Chen Q, Ge D, Xu X, Chen F, Du S, Bai Y, Liu D, Lei Y, Zhu Y, Long C, et al. Glymphatic function associates with Alzheimer\u2019s disease-signature region volumes, plasma biomarkers and white matter hyperintensity progression in cognitively unimpaired older adults. Age Ageing. 2025;54(6). https:\/\/doi.org\/10.1093\/ageing\/afaf141.","DOI":"10.1093\/ageing\/afaf141"},{"key":"8067_CR44","doi-asserted-by":"publisher","first-page":"1309482","DOI":"10.3389\/fnins.2024.1309482","volume":"18","author":"D Liu","year":"2024","unstructured":"Liu D, Lu J, Wei L, Yao M, Yang H, Lv P, Wang H, Zhu Y, Zhu Z, Zhang X, et al. Olfactory deficit: a potential functional marker across the Alzheimer\u2019s disease continuum. Front NeuroSci. 2024;18:1309482. https:\/\/doi.org\/10.3389\/fnins.2024.1309482.","journal-title":"Front NeuroSci"},{"issue":"4","key":"8067_CR45","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1177\/13872877251322539","volume":"104","author":"X Xu","year":"2025","unstructured":"Xu X, Mo X, Zhang W, Liu D, Chen Q, Lu J, Zhu Y, Chen J, Zhang X, Zhu Z, et al. Local and distant atrophy mediate the relationship between tau pathology and cognition in temporoparietal region in Alzheimer\u2019s disease. J Alzheimer\u2019s disease: JAD. 2025;104(4):1092\u2013102. https:\/\/doi.org\/10.1177\/13872877251322539.","journal-title":"J Alzheimer\u2019s disease: JAD"},{"issue":"3","key":"8067_CR46","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.jalz.2016.08.005","volume":"13","author":"CR Jack","year":"2017","unstructured":"Jack J CR, Wiste HJ, Weigand SD, Therneau TM, Lowe VJ, Knopman DS, Gunter JL, Senjem ML, Jones DT, Kantarci K, et al. Defining imaging biomarker cut points for brain aging and Alzheimer\u2019s disease. Alzheimers Dement. 2017;13(3):205\u201316. https:\/\/doi.org\/10.1016\/j.jalz.2016.08.005.","journal-title":"Alzheimers Dement"},{"key":"8067_CR47","doi-asserted-by":"crossref","unstructured":"Yu Q, Li B. Statistical methods for mediation, confounding and moderation analysis using R and SAS. Chapman and Hall\/CRC; 2022.","DOI":"10.1201\/9780429346941"},{"key":"8067_CR48","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-026-02261-9","author":"Z Zhang","year":"2026","unstructured":"Zhang Z, Li S, Xu L, Xiao S, Li Y, Huang J, Huang J, Zuo Y, Wen W, Dai Q, et al. Amyloid-\u03b2-driven glymphatic dysfunction in Alzheimer\u2019s disease model mice is driven by Ca2+-mediated increases in astrocytic cholesterol. Nat Neurosci. 2026. https:\/\/doi.org\/10.1038\/s41593-026-02261-9.","journal-title":"Nat Neurosci"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-08067-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-026-08067-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-08067-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:02:09Z","timestamp":1790971329000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-026-08067-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":48,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["8067"],"URL":"https:\/\/doi.org\/10.1007\/s00259-026-08067-y","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"assertion":[{"value":"26 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The work has not been published previously, is not under consideration for publication elsewhere. All authors have reviewed the contents of the manuscript being submitted and approved its contents. The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The WHUH study was approved by the Ethics Committee of Union Hospital Affiliated Tongji Medical College, Huazhong University of Science and Technology (2024-S0257).","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent was obtained from all individuals both from WHUH and ADNI cohorts.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The author Xiaoli Lan is an editor in this journal.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}