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This study examined whether vascular smooth muscle cell (VSMC) loss, rather than amyloidosis or neuroinflammation, underlies CVR deficits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Non\u2010contrast magnetic resonance imaging (MRI), including phase\u2010contrast and pseudo\u2010continuous arterial spin labeling, was performed in mouse models of amyloidosis (five familial Alzheimer's disease mutations [5xFAD]), VSMC degeneration (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]), and lipopolysaccharide\u2010induced neuroinflammation. Characterizations of vascular, amyloid beta, and inflammatory markers were performed for pathological assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>CVR impairment emerged only when VSMC loss was present in CADASIL mice and at older ages in 5xFAD mice (9\u201312 months). Amyloid beta deposition occurred earlier than VSMC loss or CVR decline. Neuroinflammation primarily altered baseline cerebral blood flow without affecting CVR or VSMC integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings identify VSMC degeneration as an important driver of CVR impairment independent of cerebral amyloid angiopathy or inflammation, highlighting vascular integrity as a potential therapeutic target in ADRD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71209","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:45:50Z","timestamp":1773002750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vascular smooth muscle cell loss, but not neuroinflammation, drives cerebrovascular reactivity impairment in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Xiuli","family":"Yang","sequence":"first","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguo","family":"Li","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"F. M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Research Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minmin","family":"Yao","sequence":"additional","affiliation":[{"name":"Division of Neurobiology Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Bibic","sequence":"additional","affiliation":[{"name":"F. M. 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