{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:38:50Z","timestamp":1792557530109,"version":"4.5.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":86,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Hunan Provincial Natural Science Foundation","award":["2026JJ81752"],"award-info":[{"award-number":["2026JJ81752"]}]},{"name":"Changsha Municipal Guidance Science and Technology Plan Project","award":["kzd2501107"],"award-info":[{"award-number":["kzd2501107"]}]},{"name":"Joint Foundation of Hunan University of Chinese Medicine","award":["2025XYLH020"],"award-info":[{"award-number":["2025XYLH020"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurosci"],"DOI":"10.1186\/s12868-026-01031-4","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:36:17Z","timestamp":1785116177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A latent genetic factor underlies multiple component phenotypes of cerebral small vessel disease"],"prefix":"10.1186","volume":"27","author":[{"given":"Yan","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"1031_CR1","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/S1474-4422(10)70104-6","volume":"9","author":"L Pantoni","year":"2010","unstructured":"Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689\u2013701. https:\/\/doi.org\/10.1016\/S1474-4422(10)70104-6.","journal-title":"Lancet Neurol"},{"key":"1031_CR2","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/S1474-4422(13)70060-7","volume":"12","author":"JM Wardlaw","year":"2013","unstructured":"Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013;12:483\u201397. https:\/\/doi.org\/10.1016\/S1474-4422(13)70060-7.","journal-title":"Lancet Neurol"},{"key":"1031_CR3","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1152\/physrev.00028.2024","volume":"105","author":"HS Markus","year":"2025","unstructured":"Markus HS, Joutel A. The pathogenesis of cerebral small vessel disease and vascular cognitive impairment. Physiol Rev. 2025;105:1075\u2013171. https:\/\/doi.org\/10.1152\/physrev.00028.2024.","journal-title":"Physiol Rev"},{"key":"1031_CR4","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13024-023-00640-5","volume":"18","author":"Y Inoue","year":"2023","unstructured":"Inoue Y, Shue F, Bu G, Kanekiyo T. Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer\u2019s disease. Mol neurodegeneration. 2023;18:46. https:\/\/doi.org\/10.1186\/s13024-023-00640-5.","journal-title":"Mol neurodegeneration"},{"key":"1031_CR5","doi-asserted-by":"publisher","unstructured":"Dupr\u00e9 N, Drieu A, Joutel A. Pathophysiology of cerebral small vessel disease: a journey through recent discoveries. J Clin Invest. 2024;134. https:\/\/doi.org\/10.1172\/JCI172841.","DOI":"10.1172\/JCI172841"},{"key":"1031_CR6","doi-asserted-by":"publisher","unstructured":"Hainsworth A, Markus H, Schneider J. Cerebral small vessel disease, hypertension, and vascular contributions to cognitive impairment and dementia. Hypertension. 2024;81:75\u201386. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.123.19943.","DOI":"10.1161\/HYPERTENSIONAHA.123.19943"},{"key":"1031_CR7","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1161\/STROKEAHA.123.045664","volume":"55","author":"Y Ma","year":"2024","unstructured":"Ma Y, Wang M, Chen X, Yao J, Ding Y, Gao Q, et al. Effect of the Blood Pressure and Antihypertensive Drugs on Cerebral Small Vessel Disease: A Mendelian Randomization Study. Stroke. 2024;55:1838\u201346. https:\/\/doi.org\/10.1161\/STROKEAHA.123.045664.","journal-title":"Stroke"},{"key":"1031_CR8","doi-asserted-by":"publisher","first-page":"e209666","DOI":"10.1212\/WNL.0000000000209666","volume":"103","author":"E Mui\u00f1o","year":"2024","unstructured":"Mui\u00f1o E, Carcel-Marquez J, Lluci\u00e0-Carol L, Gallego-Fabrega C, Cullell N, Lled\u00f3s M, et al. Identification of Genetic Loci Associated With Intracerebral Hemorrhage Using a Multitrait Analysis Approach. Neurology. 2024;103:e209666. https:\/\/doi.org\/10.1212\/WNL.0000000000209666.","journal-title":"Neurology"},{"key":"1031_CR9","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1212\/WNL.0000000000000837","volume":"83","author":"J Staals","year":"2014","unstructured":"Staals J, Makin S, Doubal F, Dennis M, Wardlaw J. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology. 2014;83:1228\u201334. https:\/\/doi.org\/10.1212\/WNL.0000000000000837.","journal-title":"Neurology"},{"key":"1031_CR10","doi-asserted-by":"publisher","first-page":"e0242319","DOI":"10.1371\/journal.pone.0242319","volume":"15","author":"W Ryu","year":"2020","unstructured":"Ryu W, Jeong S, Kim D. Total small vessel disease burden and functional outcome in patients with ischemic stroke. PLoS ONE. 2020;15:e0242319. https:\/\/doi.org\/10.1371\/journal.pone.0242319.","journal-title":"PLoS ONE"},{"key":"1031_CR11","doi-asserted-by":"publisher","first-page":"e70326","DOI":"10.1002\/alz.70326","volume":"21","author":"S Charisis","year":"2025","unstructured":"Charisis S, Rashid T, Dintica C, Gonzales M, Liu H, Ware JB, et al. Assessing the Global Impact of Brain Small Vessel Disease on Cognition: The Multi-Ethnic Study of Atherosclerosis. Alzheimers Dement. 2025;21:e70326. https:\/\/doi.org\/10.1002\/alz.70326.","journal-title":"Alzheimers Dement"},{"key":"1031_CR12","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1093\/brain\/awab432","volume":"145","author":"A Mishra","year":"2022","unstructured":"Mishra A, Dupla\u00e0 C, Vojinovic D, Suzuki H, Sargurupremraj M, Zilh\u00e3o N, et al. Gene-mapping study of extremes of cerebral small vessel disease reveals. as strong candidate Brain: J Neurol. 2022;145:1992\u20132007. https:\/\/doi.org\/10.1093\/brain\/awab432.","journal-title":"as strong candidate Brain: J Neurol"},{"key":"1031_CR13","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jacc.2025.11.008","volume":"87","author":"P Sachdev","year":"2026","unstructured":"Sachdev P, Bentvelzen A, Gustafson D, Hansra G, Hosoki S, Jiang J, et al. Vascular Cognitive Impairment and Dementia: Clinical Features, Neuropathology, and Biomarkers. J Am Coll Cardiol. 2026;87:52\u201376. https:\/\/doi.org\/10.1016\/j.jacc.2025.11.008.","journal-title":"J Am Coll Cardiol"},{"key":"1031_CR14","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/s41581-021-00430-6","volume":"17","author":"Z Ungvari","year":"2021","unstructured":"Ungvari Z, Toth P, Tarantini S, Prodan C, Sorond F, Merkely B, et al. Hypertension-induced cognitive impairment: from pathophysiology to public health. Nat Rev Nephrol. 2021;17:639\u201354. https:\/\/doi.org\/10.1038\/s41581-021-00430-6.","journal-title":"Nat Rev Nephrol"},{"key":"1031_CR15","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1161\/STROKEAHA.124.046249","volume":"55","author":"S Larsson","year":"2024","unstructured":"Larsson S, Chen J, Gill D, Burgess S, Yuan S. Risk Factors for Intracerebral Hemorrhage: Genome-Wide Association Study and Mendelian Randomization Analyses. Stroke. 2024;55:1582\u201391. https:\/\/doi.org\/10.1161\/STROKEAHA.124.046249.","journal-title":"Stroke"},{"key":"1031_CR16","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S1474-4422(21)00031-4","volume":"20","author":"M Traylor","year":"2021","unstructured":"Traylor M, Persyn E, Tomppo L, Klasson S, Abedi V, Bakker M, et al. Genetic basis of lacunar stroke: a pooled analysis of individual patient data and genome-wide association studies. Lancet Neurol. 2021;20:351\u201361. https:\/\/doi.org\/10.1016\/S1474-4422(21)00031-4.","journal-title":"Lancet Neurol"},{"key":"1031_CR17","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1038\/s41591-023-02268-w","volume":"29","author":"M Duperron","year":"2023","unstructured":"Duperron M, Knol M, Le GQ, Evans T, Mishra A, Tsuchida A, et al. Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease. Nat Med. 2023;29:950\u201362. https:\/\/doi.org\/10.1038\/s41591-023-02268-w.","journal-title":"Nat Med"},{"key":"1031_CR18","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1161\/CIRCGENETICS.114.000858","volume":"8","author":"B Verhaaren","year":"2015","unstructured":"Verhaaren B, Debette S, Bis J, Smith J, Ikram M, Adams H, et al. Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI. Circulation Cardiovasc Genet. 2015;8:398\u2013409. https:\/\/doi.org\/10.1161\/CIRCGENETICS.114.000858.","journal-title":"Circulation Cardiovasc Genet"},{"key":"1031_CR19","doi-asserted-by":"publisher","first-page":"e749","DOI":"10.1212\/WNL.0000000000006952","volume":"92","author":"M Traylor","year":"2019","unstructured":"Traylor M, Tozer D, Croall I, Lisiecka-Ford D, Olorunda A, Boncoraglio G, et al. Genetic variation in. is Assoc white matter hyperintensities (n = 11 226) Neurol. 2019;92:e749\u201357. https:\/\/doi.org\/10.1212\/WNL.0000000000006952.","journal-title":"is Assoc white matter hyperintensities (n = 11 226) Neurol"},{"key":"1031_CR20","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1038\/s41467-018-04362-x","volume":"9","author":"G Davies","year":"2018","unstructured":"Davies G, Lam M, Harris S, Trampush J, Luciano M, Hill W, et al. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nat Commun. 2018;9:2098. https:\/\/doi.org\/10.1038\/s41467-018-04362-x.","journal-title":"Nat Commun"},{"key":"1031_CR21","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1161\/STROKEAHA.119.027544","volume":"51","author":"N Armstrong","year":"2020","unstructured":"Armstrong N, Mather K, Sargurupremraj M, Knol M, Malik R, Satizabal C, et al. Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities. Stroke. 2020;51:2111\u201321. https:\/\/doi.org\/10.1161\/STROKEAHA.119.027544.","journal-title":"Stroke"},{"key":"1031_CR22","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/s41562-019-0566-x","volume":"3","author":"A Grotzinger","year":"2019","unstructured":"Grotzinger A, Rhemtulla M, de Ritchie VR, Mallard S, Hill T. Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits. Nat Hum Behav. 2019;3:513\u201325. https:\/\/doi.org\/10.1038\/s41562-019-0566-x.","journal-title":"Nat Hum Behav"},{"key":"1031_CR23","doi-asserted-by":"publisher","unstructured":"1000 GPC, Auton A, Brooks L, Durbin R, Garrison E, Kang H, et al. A global reference for human genetic variation. Nature. 2015;526:68\u201374. https:\/\/doi.org\/10.1038\/nature15393.","DOI":"10.1038\/nature15393"},{"key":"1031_CR24","doi-asserted-by":"publisher","unstructured":"Bulik-Sullivan B, Loh PR, Finucane HK, Ripke S, Yang J, Schizophrenia Working Group of the Psychiatric Genomics Consortium, et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet. 2015;47(3):291\u2013295. https:\/\/doi.org\/10.1038\/ng.3211.","DOI":"10.1038\/ng.3211"},{"key":"1031_CR25","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","volume":"8","author":"K Watanabe","year":"2017","unstructured":"Watanabe K, Taskesen E, van Posthuma BA. Functional mapping and annotation of genetic associations with FUMA. Nat Commun. 2017;8:1826. https:\/\/doi.org\/10.1038\/s41467-017-01261-5.","journal-title":"Nat Commun"},{"key":"1031_CR26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004219","author":"LC de Mooij","year":"2015","unstructured":"de Leeuw CA, Mooij JM, Heskes T, Posthuma D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput Biol. 2015;11(4):e1004219. https:\/\/doi.org\/10.1371\/journal.pcbi.1004219."},{"key":"1031_CR27","doi-asserted-by":"publisher","DOI":"10.1101\/2024.05.13.24307291","author":"J Rossen","year":"2024","unstructured":"Rossen J, Shi H, Strober B, Zhang M, Kanai M, McCaw Z, et al. MultiSuSiE improves multi-ancestry fine-mapping in All of Us whole-genome sequencing data. medRxiv: preprint Serv health Sci. 2024. https:\/\/doi.org\/10.1101\/2024.05.13.24307291.","journal-title":"medRxiv: preprint Serv health Sci"},{"key":"1031_CR28","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw018","author":"C Benner","year":"2016","unstructured":"Benner C, Spencer CC, Havulinna AS, Salomaa V, Ripatti S, Pirinen M. FINEMAP: efficient variable selection using summary data from genome-wide association studies. Bioinformatics. 2016;32(10):1493\u20131501. https:\/\/doi.org\/10.1093\/bioinformatics\/btw018."},{"key":"1031_CR29","doi-asserted-by":"publisher","first-page":"e1008973","DOI":"10.1371\/journal.pgen.1008973","volume":"17","author":"H Feng","year":"2021","unstructured":"Feng H, Mancuso N, Gusev A, Majumdar A, Major M, Pasaniuc B, et al. Leveraging expression from multiple tissues using sparse canonical correlation analysis and aggregate tests improves the power of transcriptome-wide association studies. PLoS Genet. 2021;17:e1008973. https:\/\/doi.org\/10.1371\/journal.pgen.1008973.","journal-title":"PLoS Genet"},{"key":"1031_CR30","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/s41588-019-0367-1","volume":"51","author":"N Mancuso","year":"2019","unstructured":"Mancuso N, Freund M, Johnson R, Shi H, Kichaev G, Gusev A, et al. Probabilistic fine-mapping of transcriptome-wide association studies. Nat Genet. 2019;51:675\u201382. https:\/\/doi.org\/10.1038\/s41588-019-0367-1.","journal-title":"Nat Genet"},{"key":"1031_CR31","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","volume":"1","author":"A Liberzon","year":"2015","unstructured":"Liberzon A, Birger C, Thorvaldsd\u00f3ttir H, Ghandi M, Mesirov J, Tamayo P. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 2015;1:417\u201325. https:\/\/doi.org\/10.1016\/j.cels.2015.12.004.","journal-title":"Cell Syst"},{"key":"1031_CR32","doi-asserted-by":"publisher","unstructured":"Timshel P, Thompson J, Pers T. Genetic mapping of etiologic brain cell types for obesity. eLife. 2020;9. https:\/\/doi.org\/10.7554\/eLife.55851.","DOI":"10.7554\/eLife.55851"},{"key":"1031_CR33","doi-asserted-by":"publisher","unstructured":"Tabula MC, et al. Overall coordination, Logistical coordination, organ collection and processing, library preparation and sequencing, computational data analysis,. single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature. 2018;562:367\u201372. https:\/\/doi.org\/10.1038\/s41586-018-0590-4.","DOI":"10.1038\/s41586-018-0590-4"},{"key":"1031_CR34","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1038\/ng.3404","volume":"47","author":"H Finucane","year":"2015","unstructured":"Finucane H, Bulik-Sullivan B, Gusev A, Trynka G, Reshef Y, Loh P, et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat Genet. 2015;47:1228\u201335. https:\/\/doi.org\/10.1038\/ng.3404.","journal-title":"Nat Genet"},{"key":"1031_CR35","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.3233\/JAD-215053","volume":"85","author":"E McGrath","year":"2022","unstructured":"McGrath E, Himali J, Levy D, Yang Q, DeCarli C, Courchesne P, et al. Plasma. Is Assoc Brain Aging Dementia: Framingham Heart Study J Alzheimer\u2019s disease: JAD. 2022;85:1657\u201366. https:\/\/doi.org\/10.3233\/JAD-215053.","journal-title":"Is Assoc Brain Aging Dementia: Framingham Heart Study J Alzheimer\u2019s disease: JAD"},{"key":"1031_CR36","doi-asserted-by":"publisher","first-page":"2264","DOI":"10.1161\/STROKEAHA.124.046544","volume":"55","author":"X Yang","year":"2024","unstructured":"Yang X, Huang M, Han F, Ni J, Zhou L, Yao M, et al. Genome-Wide Mendelian Randomization Study Reveals Druggable Genes for Cerebral Small Vessel Disease. Stroke. 2024;55:2264\u201373. https:\/\/doi.org\/10.1161\/STROKEAHA.124.046544.","journal-title":"Stroke"},{"key":"1031_CR37","doi-asserted-by":"publisher","unstructured":"Johann L, Soldati S, M\u00fcller K, Lampe J, Marini F, Klein M, et al. A20 regulates lymphocyte adhesion in murine neuroinflammation by restricting endothelial ICOSL expression in the CNS. J Clin Invest. 2023;133. https:\/\/doi.org\/10.1172\/JCI168314.","DOI":"10.1172\/JCI168314"},{"key":"1031_CR38","doi-asserted-by":"publisher","unstructured":"Das V, Narayanan S, Zhang X, Bergman O, Djordjevic D, Kronqvist M, et al. Multi-omics data integration from patients with carotid stenosis illuminates key molecular signatures of atherosclerotic instability. Genome Med. 2026;18. https:\/\/doi.org\/10.1186\/s13073-026-01601-5.","DOI":"10.1186\/s13073-026-01601-5"},{"key":"1031_CR39","doi-asserted-by":"publisher","unstructured":"Delobel V, Grenier C, Boulestreau R, Rubin S, Vaurs J, Jaspard-Vinassa B, et al. Endothelial KEAP1\/NRF2 signaling regulates blood-brain barrier integrity and cognition in mice. Commun Biol. 2026;9. https:\/\/doi.org\/10.1038\/s42003-026-09628-5.","DOI":"10.1038\/s42003-026-09628-5"},{"key":"1031_CR40","doi-asserted-by":"publisher","unstructured":"Li Y, Huang X, Guo F, Lei T, Li S, Monaghan-Nichols P, et al. TRIM65 E3 ligase targets VCAM-1 degradation to limit LPS-induced lung inflammation. J Mol Cell Biol. 2020;12:190\u2013201. https:\/\/doi.org\/10.1093\/jmcb\/mjz077.","DOI":"10.1093\/jmcb\/mjz077"},{"key":"1031_CR41","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1093\/brain\/awac290","volume":"146","author":"Y Yang","year":"2023","unstructured":"Yang Y, Knol M, Wang R, Mishra A, Liu D, Luciano M, et al. Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI. Brain. 2023;146:492\u2013506. https:\/\/doi.org\/10.1093\/brain\/awac290.","journal-title":"Brain"},{"key":"1031_CR42","doi-asserted-by":"publisher","first-page":"3176","DOI":"10.1093\/brain\/awz233","volume":"142","author":"J Chung","year":"2019","unstructured":"Chung J, Marini S, Pera J, Norrving B, Jimenez-Conde J, Roquer J, et al. Genome-wide association study of cerebral small vessel disease reveals established and novel loci. Brain. 2019;142:3176\u201389. https:\/\/doi.org\/10.1093\/brain\/awz233.","journal-title":"Brain"},{"key":"1031_CR43","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1212\/WNL.0000000000002263","volume":"86","author":"M Traylor","year":"2016","unstructured":"Traylor M, Zhang C, Adib-Samii P, Devan W, Parsons O, Lanfranconi S, et al. Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke. Neurology. 2016;86:146\u201353. https:\/\/doi.org\/10.1212\/WNL.0000000000002263.","journal-title":"Neurology"},{"key":"1031_CR44","doi-asserted-by":"publisher","unstructured":"Lecce L, Xu Y, V\u2019Gangula B, Chandel N, Pothula V, Caudrillier A, et al. Histone deacetylase 9 promotes endothelial-mesenchymal transition and an unfavorable atherosclerotic plaque phenotype. J Clin Invest. 2021;131. https:\/\/doi.org\/10.1172\/JCI131178.","DOI":"10.1172\/JCI131178"},{"key":"1031_CR45","doi-asserted-by":"publisher","first-page":"632","DOI":"10.7150\/thno.103449","volume":"15","author":"J Li","year":"2025","unstructured":"Li J, Wang C, Zhang Y, Huang Y, Shi Z, Zhang Y, et al. Orchestrating the frontline: HDAC3-miKO recruits macrophage reinforcements for accelerated myelin debris clearance after stroke. Theranostics. 2025;15:632\u201355. https:\/\/doi.org\/10.7150\/thno.103449.","journal-title":"Theranostics"},{"key":"1031_CR46","doi-asserted-by":"publisher","first-page":"e210063","DOI":"10.1212\/WNL.0000000000210063","volume":"103","author":"M Real","year":"2024","unstructured":"Real M, Falcione S, Boghozian R, Clarke M, Todoran R, St PA, et al. Endothelial Cell Senescence Effect on the Blood-Brain Barrier in Stroke and Cognitive Impairment. Neurology. 2024;103:e210063. https:\/\/doi.org\/10.1212\/WNL.0000000000210063.","journal-title":"Neurology"},{"key":"1031_CR47","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.neuron.2025.10.018","volume":"114","author":"S Schaeffer","year":"2026","unstructured":"Schaeffer S, Pacholko A, Santisteban M, Ahn S, Racchumi G, Wang G, et al. Hypertension-induced neurovascular and cognitive dysfunction at single-cell resolution. Neuron. 2026;114:422\u2013e4437. https:\/\/doi.org\/10.1016\/j.neuron.2025.10.018.","journal-title":"Neuron"},{"key":"1031_CR48","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s11357-021-00493-0","volume":"44","author":"DM van Schram","year":"2022","unstructured":"van Schram DM, Jansen M, Backes J, Houben W, Berendschot A. Extracerebral microvascular dysfunction is related to brain MRI markers of cerebral small vessel disease: The Maastricht Study. GeroScience. 2022;44:147\u201357. https:\/\/doi.org\/10.1007\/s11357-021-00493-0.","journal-title":"GeroScience"},{"key":"1031_CR49","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1111\/jgs.15240","volume":"66","author":"M Georgakis","year":"2018","unstructured":"Georgakis M, Chatzopoulou D, Tsivgoulis G, Petridou E. Albuminuria and Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis. J Am Geriatr Soc. 2018;66:509\u201317. https:\/\/doi.org\/10.1111\/jgs.15240.","journal-title":"J Am Geriatr Soc"},{"key":"1031_CR50","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","volume":"25","author":"D Nation","year":"2019","unstructured":"Nation D, Sweeney M, Montagne A, Sagare A, D\u2019Orazio L, Pachicano M, et al. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat Med. 2019;25:270\u20136. https:\/\/doi.org\/10.1038\/s41591-018-0297-y.","journal-title":"Nat Med"},{"key":"1031_CR51","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1038\/s41591-020-0886-4","volume":"26","author":"J Blanchard","year":"2020","unstructured":"Blanchard J, Bula M, Davila-Velderrain J, Akay L, Zhu L, Frank A, et al. Reconstruction of the human blood-brain barrier in vitro reveals a pathogenic mechanism of. pericytes Nat Med. 2020;26:952\u201363. https:\/\/doi.org\/10.1038\/s41591-020-0886-4.","journal-title":"pericytes Nat Med"},{"key":"1031_CR52","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1097\/JS9.0000000000002228","volume":"111","author":"J Wang","year":"2025","unstructured":"Wang J, Xu W, Dove A, Salami A, Yang W, Ma X, et al. Influence of lung function on macro- and micro-structural brain changes in mid- and late-life. Int J Surg (London England). 2025;111:2467\u201377. https:\/\/doi.org\/10.1097\/JS9.0000000000002228.","journal-title":"Int J Surg (London England)"},{"key":"1031_CR53","doi-asserted-by":"publisher","unstructured":"Patel HN, Aggarwal NT, Rao A, Bryant E, Sanghani R, Byrnes M, et al. Microvascular disease and small-vessel disease: the nexus of multiple diseases of women. J Womens Health (Larchmt). 2020;29(6):770\u2013779. https:\/\/doi.org\/10.1089\/jwh.2019.7826.","DOI":"10.1089\/jwh.2019.7826"},{"key":"1031_CR54","doi-asserted-by":"publisher","first-page":"e209540","DOI":"10.1212\/WNL.0000000000209540","volume":"103","author":"P Nash","year":"2024","unstructured":"Nash P, Fandler-H\u00f6fler S, Ambler G, Zhang W, Ozkan H, Locatelli M, et al. Associations of Cerebral Small Vessel Disease and Chronic Kidney Disease in Patients With Acute Intracerebral Hemorrhage: A Cross-Sectional Study. Neurology. 2024;103:e209540. https:\/\/doi.org\/10.1212\/WNL.0000000000209540.","journal-title":"Neurology"},{"key":"1031_CR55","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s12974-023-02703-2","volume":"20","author":"C Fang","year":"2023","unstructured":"Fang C, Lau W, Sun J, Chang R, Vallejo A, Lee D, et al. Chronic kidney disease promotes cerebral microhemorrhage formation. J Neuroinflamm. 2023;20:51. https:\/\/doi.org\/10.1186\/s12974-023-02703-2.","journal-title":"J Neuroinflamm"},{"key":"1031_CR56","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.neuron.2024.09.017","volume":"113","author":"L Jiang-Xie","year":"2025","unstructured":"Jiang-Xie L, Drieu A, Kipnis J. Waste clearance shapes aging brain health. Neuron. 2025;113:71\u201381. https:\/\/doi.org\/10.1016\/j.neuron.2024.09.017.","journal-title":"Neuron"},{"key":"1031_CR57","doi-asserted-by":"publisher","first-page":"118257","DOI":"10.1016\/j.neuroimage.2021.118257","volume":"238","author":"W Zhang","year":"2021","unstructured":"Zhang W, Zhou Y, Wang J, Gong X, Chen Z, Zhang X, et al. Glymphatic clearance function in patients with cerebral small vessel disease. NeuroImage. 2021;238:118257. https:\/\/doi.org\/10.1016\/j.neuroimage.2021.118257.","journal-title":"NeuroImage"}],"container-title":["BMC Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12868-026-01031-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12868-026-01031-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12868-026-01031-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:47:10Z","timestamp":1792554430000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12868-026-01031-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1031"],"URL":"https:\/\/doi.org\/10.1186\/s12868-026-01031-4","relation":{"references":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1004219","asserted-by":"subject"},{"id-type":"doi","id":"10.1093\/bioinformatics\/btw018","asserted-by":"subject"}]},"ISSN":["1471-2202"],"issn-type":[{"value":"1471-2202","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"assertion":[{"value":"13 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was conducted exclusively using publicly available GWAS summary statistics. No individual-level data were accessed or analyzed. All original GWAS included in this study had received ethical approval and informed consent from their respective institutional review boards. No additional ethical approval was required for the present analyses.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"48"}}