{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:41:57Z","timestamp":1785426117870,"version":"3.56.0"},"posted":{"date-parts":[[2025,12,3]]},"group-title":"Bioengineering","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01 AG081932"],"award-info":[{"award-number":["R01 AG081932"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P41 EB031771"],"award-info":[{"award-number":["P41 EB031771"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>Cerebrovascular reactivity (CVR) impairment is a key feature of Alzheimer\u2019s disease (AD), but its mechanistic basis remains unclear. 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-contrast MRI, including phase-contrast and pseudo-continuous arterial spin labeling, was performed in mouse models of amyloidosis (5xFAD), VSMC degeneration (CADASIL), and lipopolysaccharide-induced neuroinflammation. Characterization of vascular, amyloid-\u03b2, 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-\u03b2 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 AD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Cerebrovascular reactivity (CVR) impairment occurred in 5xFAD mice only when vascular smooth muscle cell (VSMC) loss was present<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>5xFAD mice exhibited prominent parenchymal but minimal vascular amyloid-\u03b2 deposition<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>VSMC developmental deficiency resulted in CVR impairment in a small-vessel disease (SVD) model<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Neuroinflammation primarily altered baseline cerebral blood flow (CBF) without affecting CVR<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.01.691642","type":"posted-content","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T12:49:50Z","timestamp":1765198190000},"source":"Crossref","is-referenced-by-count":1,"title":["Vascular smooth muscle cell loss, but not neuroinflammation, drives cerebrovascular reactivity impairment in Alzheimer\u2019s 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