{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:15:14Z","timestamp":1779894914191,"version":"3.53.1"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MHLW Research on Dementia Program","award":["JPMH24GB1001"],"award-info":[{"award-number":["JPMH24GB1001"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["20K20497"],"award-info":[{"award-number":["20K20497"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["23K18262"],"award-info":[{"award-number":["23K18262"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Autopsy studies have shown that Alzheimer\u2019s disease (AD) often coexists with cerebrovascular injury, affecting cognitive outcomes and the effectiveness of anti-amyloid-beta (A\u03b2) drugs. No fluid biomarkers of cerebrovascular injury have been identified yet. We investigated the association between white matter hyperintensities (WMH) severity and fluid biomarkers, including cerebrospinal fluid (CSF) neurofilament light chain and plasma placental growth factor (PlGF) levels. This study included 242 patients from memory clinics. Magnetic resonance imaging (MRI), CSF, and plasma samples were collected. Patients were classified as AD+ or non-AD based on the CSF A\u03b242\/A\u03b240 ratio. In the discovery cohort (79 AD+ and 20 non-AD patients with 3D-T1 images), we analyzed the association between WMH volume and plasma PlGF. In the validation cohort (54 AD+ patients without 3D-T1 images), we analyzed the association between WMH grading and plasma PlGF. Among AD+ patients in the discovery cohort, plasma PlGF levels remained significantly associated with WMH volume and grading after adjusting for age, sex, and global cognition. Among the AD+ patients in the validation cohort, the high-PlGF (above median) group had significantly greater WMH volumes and a higher number of patients with a high WMH grading than the low-PlGF (below median) group. Plasma PlGF is a promising marker of cerebrovascular injury in AD.<\/jats:p>","DOI":"10.3390\/biom15101367","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T09:35:49Z","timestamp":1758879349000},"page":"1367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association of Plasma Placental Growth Factor with White Matter Hyperintensities in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Kazuya","family":"Igarashi","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata 951-8585, Japan"},{"name":"Department of Neurology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7958-8991","authenticated-orcid":false,"given":"Tamao","family":"Tsukie","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata 951-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Washiyama","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Niigata Rinko Hospital, Niigata 950-8725, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Onda","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Niigata Neurosurgical Hospital, Niigata 950-1101, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Miyagi","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Tokyo Medical University, Tokyo 160-8402, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoya","family":"Inagawa","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Tokyo Medical University, Tokyo 160-8402, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Tokyo Medical University, Tokyo 160-8402, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2508-9649","authenticated-orcid":false,"given":"Akinori","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata 951-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3354-5472","authenticated-orcid":false,"given":"Osamu","family":"Onodera","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8828-8085","authenticated-orcid":false,"given":"Takeshi","family":"Ikeuchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata 951-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2178-0769","authenticated-orcid":false,"given":"Kensaku","family":"Kasuga","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata 951-8585, Japan"},{"name":"Department of Diagnostic Innovation Science, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1001\/jama.2023.13239","article-title":"Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial","volume":"330","author":"Sims","year":"2023","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in Early Alzheimer\u2019s Disease","volume":"388","author":"Swanson","year":"2023","journal-title":"N. 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