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However, their clinical application remains challenging due to insufficient specificity, heterogeneity, and technical limitations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we report that vessel- and cortical layer-specific parameters exhibit promising diagnostic sensitivity for neurovascular impairments in an AD\/ADRD mouse model, apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) 4 knock-in (KI), compared to\n                      <jats:italic>APOE3<\/jats:italic>\n                      -KI at 12 months of age. Using two in vivo imaging modalities, 3D capillary-resolution optical Doppler tomography and laser speckle contrast imaging, we measured 36 morphological and functional vascular parameters and evaluated their diagnostic performance using a machine-learning Support Vector Machine classifier.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>APOE4<\/jats:italic>\n                      mice showed significant alterations including reduced venular and arterial cerebral blood flow velocities and diameters, increased vascular tortuosity, layer-dependent decreases in vascular density, and impaired cerebrovascular reactivity. Venule- and microcirculation-related parameters and dynamic vasoactivity to brain stimuli demonstrated high diagnostic accuracy (~\u200990%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Together, these findings provide in vivo evidence for early, cortical layer-specific neurovascular dysfunction caused by\n                      <jats:italic>APOE4<\/jats:italic>\n                      that increases the susceptibility to dementia and highlight the potential of combining neurovascular biomarkers from optical imaging with AI-based classifier for identification of increased AD\/ADRD risk.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40035-025-00530-4","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T03:10:13Z","timestamp":1766373013000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cortical layer multi-parameter analysis of neurovascular impairments in AD\/ADRD rodent model with in vivo optical imaging"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9970-7069","authenticated-orcid":false,"given":"Hyomin","family":"Jeong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxiang","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wensheng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora D.","family":"Volkow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibin","family":"Ling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Congwu","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7635-1443","authenticated-orcid":false,"given":"Yingtian","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"issue":"16","key":"530_CR1","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","volume":"278","author":"LA Farrer","year":"1997","unstructured":"Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. 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