{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:17:44Z","timestamp":1790612264734,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Science and Technology Committee Project","award":["23ZR1439200"],"award-info":[{"award-number":["23ZR1439200"]}]},{"name":"Shanghai Science and Technology Committee Project","award":["2022YFA1603604 [ZZ]"],"award-info":[{"award-number":["2022YFA1603604 [ZZ]"]}]},{"name":"Shanghai Science and Technology Committee Project","award":["82271320 [ZZ]"],"award-info":[{"award-number":["82271320 [ZZ]"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["23ZR1439200"],"award-info":[{"award-number":["23ZR1439200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2022YFA1603604 [ZZ]"],"award-info":[{"award-number":["2022YFA1603604 [ZZ]"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["82271320 [ZZ]"],"award-info":[{"award-number":["82271320 [ZZ]"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["23ZR1439200"],"award-info":[{"award-number":["23ZR1439200"]}],"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":["2022YFA1603604 [ZZ]"],"award-info":[{"award-number":["2022YFA1603604 [ZZ]"]}],"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":["82271320 [ZZ]"],"award-info":[{"award-number":["82271320 [ZZ]"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with Alzheimer\u2019s disease (AD) often present with imaging features indicative of small-vessel injury, among which, white-matter hyperintensities (WMHs) are the most prevalent. However, the underlying mechanism of the association between AD and small-vessel injury is still obscure. The aim of this study is to investigate the mechanism of small-vessel injury in AD. Differential gene expression analyses were conducted to identify the genes related to WMHs separately in mild cognitive impairment (MCI) and cognitively normal (CN) subjects from the ADNI database. The WMH-related genes identified in patients with MCI were considered to be associated with small-vessel injury in early AD. Functional enrichment analyses and a protein\u2013protein interaction (PPI) network were performed to explore the pathway and hub genes related to the mechanism of small-vessel injury in MCI. Subsequently, the Boruta algorithm and support vector machine recursive feature elimination (SVM-RFE) algorithm were performed to identify feature-selection genes. Finally, the mechanism of small-vessel injury was analyzed in MCI from the immunological perspectives; the relationship of feature-selection genes with various immune cells and neuroimaging indices were also explored. Furthermore, 5\u00d7FAD mice were used to demonstrate the genes related to small-vessel injury. The results of the logistic regression analyses suggested that WMHs significantly contributed to MCI, the early stage of AD. A total of 276 genes were determined as WMH-related genes in patients with MCI, while 203 WMH-related genes were obtained in CN patients. Among them, only 15 genes overlapped and were thus identified as the crosstalk genes. By employing the Boruta and SVM-RFE algorithms, CD163, ALDH3B1, MIR22HG, DTX2, FOLR2, ALDH2, and ZNF23 were recognized as the feature-selection genes linked to small-vessel injury in MCI. After considering the results from the PPI network, CD163 was finally determined as the critical WMH-related gene in MCI. The expression of CD163 was correlated with fractional anisotropy (FA) values in regions that are vulnerable to small-vessel injury in AD. The immunostaining and RT-qPCR results from the verifying experiments demonstrated that the indicators of small-vessel injury presented in the cortical tissue of 5\u00d7FAD mice and related to the upregulation of CD163 expression. CD163 may be the most pivotal candidates related to small-vessel injury in early AD.<\/jats:p>","DOI":"10.3390\/ijms25042293","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T12:09:27Z","timestamp":1707912567000},"page":"2293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["CD163-Mediated Small-Vessel Injury in Alzheimer\u2019s Disease: An Exploration from Neuroimaging to Transcriptomics"],"prefix":"10.3390","volume":"25","author":[{"given":"Yuewei","family":"Chen","sequence":"first","affiliation":[{"name":"Health Management Center, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"},{"name":"Department of Neurology, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"},{"name":"Renji-UNSW CHeBA (Centre for Healthy Brain Ageing of University of New South Wales) Neurocognitive Center, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiwen","family":"Lu","sequence":"additional","affiliation":[{"name":"Health Management Center, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"},{"name":"Renji-UNSW CHeBA (Centre for Healthy Brain Ageing of University of New South Wales) Neurocognitive Center, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengju","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Health Management Center, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"},{"name":"Department of Neurology, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"},{"name":"Renji-UNSW CHeBA (Centre for Healthy Brain Ageing of University of New South Wales) Neurocognitive Center, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwan","family":"Liu","sequence":"additional","affiliation":[{"name":"Health Management Center, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Xu","sequence":"additional","affiliation":[{"name":"Health Management Center, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"},{"name":"Department of Neurology, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"},{"name":"Renji-UNSW CHeBA (Centre for Healthy Brain Ageing of University of New South Wales) Neurocognitive Center, Renji Hospital of Medical School, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e661","DOI":"10.1016\/S2468-2667(20)30185-7","article-title":"Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: A cross-sectional study","volume":"5","author":"Jia","year":"2020","journal-title":"Lancet Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-pathol-020712-163927","article-title":"Emerging concepts in Alzheimer\u2019s disease","volume":"10","author":"Vinters","year":"2015","journal-title":"Annu. 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