{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:02:15Z","timestamp":1782280935510,"version":"3.54.5"},"posted":{"date-parts":[[2025,2,6]]},"group-title":"Neuroscience","reference-count":77,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Health","award":["R01 AG065836"],"award-info":[{"award-number":["R01 AG065836"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Global reductions in cerebral blood flow (CBF) are among the earliest and most consistent abnormalities observed in Alzheimer\u2019s disease (AD), preceding both cortical plaque formation and cognitive decline. While the pial arterial network\u2014a critical supplier of intracortical perfusion\u2014has been overlooked in this context, it may play a pivotal role in early vascular pathology. Here, we report extensive cerebral amyloid angiopathy (CAA) within the pial artery and arteriole network in the J20 (PDGF-APPSw, Ind) mouse model of AD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using premortem delivery of Methoxy-XO4 to label A\u03b2, and arterial vascular labeling, we assessed A\u03b2 burden on the pial artery\/arteriole network and cerebral blood flow in aged male and female WT and J20 AD mice.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We show that 12-month-old J20 mice exhibit significant A\u03b2 deposition across major leptomeningeal arteries (ACA, MCA) and pial collaterals, with \u223c40% vessel coverage in males and \u223c20% in females\u2014substantially exceeding A\u03b2 levels in cortical or hippocampal vessels. This vascular A\u03b2 burden was accompanied by compensatory enlargement and increased tortuosity of pial collateral vessels. Yet, despite this apparent remodeling, CBF was reduced by \u223c15% in J20 mice, and this decline was significantly associated with leptomeningeal CAA burden.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This is the first study to comprehensively characterize meningeal arterial A\u03b2 accumulation in a preclinical model of vascular AD, mirroring recent observations in early-stage human disease. Our findings implicate meningeal CAA as a potential driver of early CBF disruption and suggest that pial collateral remodeling may reflect a compensatory response to vascular insufficiency. Moreover, we identify robust sex differences in CAA burden, paralleling sex-specific patterns of parenchymal A\u03b2 pathology in humans. These results highlight the leptomeningeal vasculature as a novel and understudied locus for early AD pathology and a potential therapeutic target to preserve cerebrovascular integrity.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.02.05.635937","type":"posted-content","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:24Z","timestamp":1738886424000},"source":"Crossref","is-referenced-by-count":0,"title":["Meningeal vascular A\u03b2 deposition associates with cerebral hypoperfusion and compensatory collateral remodeling"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2054-2320","authenticated-orcid":false,"given":"Alexandra M.","family":"Kaloss","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, 24061"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3102-0667","authenticated-orcid":false,"given":"Jack 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